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1.
Homeopathy ; 113(2): 86-97, 2024 May.
Article in English | MEDLINE | ID: mdl-37604183

ABSTRACT

BACKGROUND: Ferrum phosphoricum (FP) has been used by traditional medicine practitioners for various ailments since ancient times. However, scientific evidence on the safety of FP is still unavailable. Thus, the current study aimed to investigate the acute and sub-acute oral toxicity of homeopathic FP in experimental rats. METHODS: In an acute toxicity investigation, a single dose of 2,000 µL/kg of FP 6c, 30c and 200c was administered to female Wistar rats, which were monitored for up to 14 days according to the Organization for Economic Cooperation and Development (OECD) guideline 423. For a sub-acute toxicity study, FP 6c, 30c and 200c (200 µL/kg) were administered to male and female rats for 28 days as per the OECD guideline 407. All the animals were observed for mortality, clinical signs and body weight during the study. At the end of the experiment, hematological, biochemical and histopathological assessments were performed. RESULTS: During the acute toxicity study, no mortality was observed in rats administered with FP, and thus the median lethal dose (LD50) was identified as >2,000 µL/kg. In the sub-acute study, no mortality or adverse clinical signs were noticed with FP treatment. Moreover, weekly body weight gain was normal. Hematological and biochemical investigations revealed no abnormalities. Furthermore, histological analysis of FP-treated rats' vital organs revealed no pathological changes. CONCLUSION: Overall, our findings imply that FP 6c, 30c and 200c potencies are safe and do not cause toxicity when given orally to Wistar albino rats for an extended period at a dose of 200 µL/kg.


Subject(s)
Homeopathy , Rats , Female , Male , Animals , Rats, Wistar , Toxicity Tests, Acute , Toxicity Tests, Subchronic , Body Weight , Plant Extracts
2.
Homeopathy ; 113(1): 4-15, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37517405

ABSTRACT

INTRODUCTION: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes. OBJECTIVE: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro. METHODS: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed. RESULTS: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface (p = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature. CONCLUSION: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies.


Subject(s)
Homeopathy , Lipopolysaccharides , Rats , Animals , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Aspirin/pharmacology , Toll-Like Receptor 4/metabolism , Macrophages , Cytokines , Water
3.
Homeopathy ; 113(1): 25-31, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37406672

ABSTRACT

BACKGROUND: Bovine mastitis is characterized by an inflammatory process in the mammary gland and represents one of the main diseases affecting a dairy herd. Management of mastitis is most commonly via antibiotics, but the rising incidence of multiple antibiotic resistance (MAR) means that additional options are needed. Homeopathic products can be administered in dairy farming for a range of clinical reasons and may be preferential due to the absence of residues. OBJECTIVES: The aim of this study was to assess the potential of a novel homeopathic complex medicine in managing bovine mastitis. METHODS: Twenty-four lactating Holstein cows with mastitis were divided into two groups: the homeopathic complex group received a homeopathic complex daily for 60 days at a dose of 20 g/d; the placebo group received the calcium carbonate vehicle without homeopathic medicines at the same dose and repetition. The main outcome measure was somatic cell count (SCC; cells/mL), with additional outcome measures including milk production (kg/d), milk constituents (percentage of protein, fat, lactose and total milk solids), and serum levels of cortisol, glucose, ammonia and lactic acid. All outcomes were measured at the beginning of the study and after 30 and 60 days. Milk samples were also collected from all animals at the beginning of the study, confirming a high (>0.2) MAR index for isolated bacterial cultures. RESULTS: Assessment of SCC showed a statistically significant difference favoring the homeopathic complex versus placebo group at day 60. A reduction in serum cortisol levels and an increase in fat, lactose and total milk solids in animals treated with the homeopathic complex at day 60 were also seen. Other outcome measures did not show statistically significant inter-group differences. CONCLUSION: The results of this non-randomized, open-label, placebo-controlled trial suggest the potential for a novel homeopathic complex medicine in management of multiple antibiotic-resistant bovine mastitis, thus offering dairy farmers an additional option to antibiotics and making dairy products safer for consumer health and milk production more sustainable.


Subject(s)
Homeopathy , Mastitis, Bovine , Materia Medica , Animals , Cattle , Female , Anti-Bacterial Agents/pharmacology , Hydrocortisone , Lactation , Lactose , Mastitis, Bovine/drug therapy , Mastitis, Bovine/epidemiology , Mastitis, Bovine/microbiology , Materia Medica/pharmacology
4.
Homeopathy ; 113(2): 80-85, 2024 May.
Article in English | MEDLINE | ID: mdl-37652040

ABSTRACT

BACKGROUND: Mastitis-metritis-agalactia (MMA) syndrome occurs in the first days post-partum and causes piglet losses mainly due to malnutrition. One possibility for prophylaxis of MMA is via homeopathy. In this veterinary study, the effectiveness of a prophylactic administration of homeopathic remedies for the prevention of the occurrence of MMA in swine was evaluated. METHODS: In a randomised and blinded study, 60 sows were examined. Sows were randomly distributed in two groups: the experimental group (CL/LL) received a prophylactic administration of the complex homeopathic remedies Caulophyllum Logoplex and Lachesis Logoplex, and the placebo group was administered a sodium chloride (NaCl) solution in the same injection scheme as the experimental group. Clinical signs of MMA, behavioural changes, as well as production parameters, were recorded beginning with the day of farrowing until 5 days post-partum. RESULTS: The treatment group showed no significant effect on the occurrence of MMA in sows (CL/LL: 56.67% MMA positive sows; NaCl: 53.53% MMA positive sows). Treatment group had also no significant effect on health parameters (vaginal discharge, raised rectal temperature, shortage of milk) or behavioural parameters (impaired feeding behaviour and impaired general condition). For the production parameter average weight gain, statistically significant effects in the treatment group were detected. CONCLUSIONS: Prophylaxis with the homeopathic remedies Caulophyllum Logoplex and Lachesis Logoplex showed neither an improvement in MMA prevention nor an improvement in health parameters or behavioural traits in the present herd of sows.


Subject(s)
Caulophyllum , Endometritis , Homeopathy , Lactation Disorders , Mastitis , Materia Medica , Swine Diseases , Humans , Animals , Swine , Female , Mastitis/drug therapy , Mastitis/prevention & control , Mastitis/etiology , Materia Medica/therapeutic use , Sodium Chloride/therapeutic use , Endometritis/epidemiology , Endometritis/etiology , Endometritis/veterinary , Swine Diseases/drug therapy , Swine Diseases/epidemiology , Swine Diseases/etiology , Lactation Disorders/drug therapy , Lactation Disorders/prevention & control , Lactation Disorders/etiology
5.
An Acad Bras Cienc ; 95(4): e20190284, 2023.
Article in English | MEDLINE | ID: mdl-38055599

ABSTRACT

Studies and innovations on alternative feed additives, especially on homeopathic remedies have been highlighted in order to replace or reduce the use of antibiotics in pig production. This paper aimed to assess the addition of homeopathic products in pig diet and their effects on the growth performance, serum metabolites, nutrient and energy digestibility, carcass traits and meat quality. A total of 60 immunocastrated male pigs, weighing on average 30.91 ± 0.95 kg, were distributed in two treatments, 10 replicates and three animals/experimental unit. There was no effect (P≥0.05) of treatment on the growth performance and serum metabolites. The percentage of acid-insoluble ash recovered in the diet was greater (P≤0.01) in diets containing homeopathic products. The apparent digestible energy of diets containing homeopathic products was reduced (P≤0.01) in the growing phase and reduced (P≤0.01) the apparent digestibility coefficients of dry matter, crude protein, soluble neutral and acid detergent fibers, and gross energy in the growing and finishing phases. Pig that received diets with homeopathic products had higher (P≤0.05) amount of meat, percentage of meat and marbling. The use of homeopathic products in diets improves the percentage and quality of meat, as well as the marbling of the pig carcass, maintaining the performance.


Subject(s)
Materia Medica , Male , Swine , Animals , Animal Feed/analysis , Diet/veterinary , Nutrients , Meat , Animal Nutritional Physiological Phenomena
6.
Int J Mol Sci ; 24(11)2023 May 30.
Article in English | MEDLINE | ID: mdl-37298430

ABSTRACT

Glyphosate is an herbicide widely used in agriculture but can present chronic toxicity in low concentrations. Artemia salina is a common bio-indicator of ecotoxicity; it was used herein as a model to evaluate the effect of highly diluted-succussed glyphosate (potentized glyphosate) in glyphosate-based herbicide (GBH) exposed living systems. Artemia salina cysts were kept in artificial seawater with 0.02% glyphosate (corresponding to 10% lethal concentration or LC10) under constant oxygenation, luminosity, and controlled temperature, to promote hatching in 48 h. Cysts were treated with 1% (v/v) potentized glyphosate in different dilution levels (Gly 6 cH, 30 cH, 200 cH) prepared the day before according to homeopathic techniques, using GBH from the same batch. Controls were unchallenged cysts, and cysts treated with succussed water or potentized vehicle. After 48 h, the number of born nauplii per 100 µL, nauplii vitality, and morphology were evaluated. The remaining seawater was used for physicochemical analyses using solvatochromic dyes. In a second set of experiments, Gly 6 cH treated cysts were observed under different degrees of salinity (50 to 100% seawater) and GBH concentrations (zero to LC 50); hatching and nauplii activity were recorded and analyzed using the ImageJ 1.52, plug-in Trackmate. The treatments were performed blind, and the codes were revealed after statistical analysis. Gly 6 cH increased nauplii vitality (p = 0.01) and improved the healthy/defective nauplii ratio (p = 0.005) but delayed hatching (p = 0.02). Overall, these results suggest Gly 6cH treatment promotes the emergence of the more GBH-resistant phenotype in the nauplii population. Also, Gly 6cH delays hatching, another useful survival mechanism in the presence of stress. Hatching arrest was most marked in 80% seawater when exposed to glyphosate at LC10. Water samples treated with Gly 6 cH showed specific interactions with solvatochromic dyes, mainly Coumarin 7, such that it appears to be a potential physicochemical marker for Gly 6 cH. In short, Gly 6 cH treatment appears to protect the Artemia salina population exposed to GBH at low concentrations.


Subject(s)
Cysts , Herbicides , Animals , Artemia , Herbicides/toxicity , Water/pharmacology , Glyphosate
7.
Homeopathy ; 112(4): 226-239, 2023 11.
Article in English | MEDLINE | ID: mdl-36929496

ABSTRACT

BACKGROUND: Clinical observational studies are an important methodological approach in human and veterinary research, examining and describing treatment experience with good external validity. There are currently few observational studies in the field of homeopathic veterinary medicine. AIM: The aim of the study was to develop recommendations for designing, conducting and reporting observational studies in homeopathic veterinary medicine. MATERIALS AND METHODS: A literature review was performed using various search strategies for identifying guidelines and checklist tools relevant for observational studies, veterinary research and homeopathy. Useful guidelines were selected. Prior recommendations for designing and conducting observational studies in human homeopathic medicine were supplemented with recommendations for homeopathic veterinary medicine that were evaluated by an expert panel. RESULTS: The veterinary extension of the Strengthening the Reporting of Observational Studies in Epidemiology - Veterinary (STROBE-Vet) statement was identified as a useful tool to improve the reporting quality of observational studies, and it has been supplemented here with additional recommendations that are applicable to homeopathy. STROBE-Vet is complemented in the literature by several reports, checklists and guidelines on veterinary medicine in general, such as the Checklist for One Health Epidemiological Reporting of Evidence (COHERE) and the Animal Health Surveillance Reporting Guidelines (AHSURED). Identified items that related to laboratory animal research were excluded as non-relevant to our study. CONCLUSION: Clinical observational studies are an important methodological approach, having currently unrealized potential in the field of homeopathic veterinary medicine. With relatively minor adjustments, the practical guidelines and checklists available to researchers in designing, conducting and reporting observational studies in human homeopathic medicine have been adapted for homeopathic veterinary medicine, for which high quality can be assured by implementing recommendations such as those in STROBE-Vet. With the emergence of the One Health concept, the COHERE checklist can be viewed with growing significance.


Subject(s)
Homeopathy , Animals , Humans , Research Report
8.
Homeopathy ; 112(4): 275-279, 2023 11.
Article in English | MEDLINE | ID: mdl-36781155

ABSTRACT

BACKGROUND: Folliculinum is a homeopathic sarcode medication that is mainly used for regulating the estrous cycle and reproductive function. In snakes, it is common to observe low frequencies of reproduction. Ovulation is related to follicular size and morphology, and follicle homogeneity may indicate the absence of problems such as dystocia (egg retention) or follicular stasis. OBJECTIVE: The objective of the present study was to report on follicular stage changes in two ball pythons, Python regius (Shaw, 1802), which were treated using Folliculinum 6cH in a zoological park setting. METHODS: Two female pythons - one weighing 2.8 kg, the other weighing 2.5 kg, and neither with a history of reproduction - were examined by ultrasound to enable viewing of ovarian follicles in different phases and sizes. Folliculinum 6cH, two globules diluted in 200 mL of water, was administered, targeted to the eyes and nostril regions. RESULTS: Even given the slow metabolism of reptiles, ultrasound revealed an improvement in follicle homogeneity between 6 and 15 days after the start of homeopathy in both snakes; there was also improved weight gain in both animals. The MOdified NARanjo Criteria for Homeopathy (MONARCH) score was +8 in each of the cases, suggesting a causal relationship between the use of homeopathic medicine and clinical outcome. CONCLUSION: Folliculinum 6cH may have promoted stabilization of follicle size and enabled folliculogenesis in two ball pythons.


Subject(s)
Boidae , Homeopathy , Animals , Female , Boidae/physiology , Ovarian Follicle
9.
Homeopathy ; 112(3): 198-204, 2023 08.
Article in English | MEDLINE | ID: mdl-36328190

ABSTRACT

BACKGROUND AND AIMS: Penguins are seabirds that manifest physiological and immunological alterations during the reproductive season. The objectives of this study were to evaluate the laboratory parameters of male and female Magellanic penguins and to determine the penguins' hematological response to homeopathic medicines during that reproductive period. METHODS: Penguins (N = 18), kept under human care in a zoological park setting, were evaluated during the reproductive period and were divided randomly into two groups: a group subjected to treatment with Echinacea angustifolia 6cH and Avena sativa 6cH (N = 8; four breeding couples), and a placebo control group (N = 10; five breeding couples). The investigators were blinded to treatment allocation. Two-way ANOVA was performed to determine whether the experimental group (control or verum) and the sex of the animal had any significant effect on the variation of each hematological parameter between the samples. One-way ANOVA was performed on hematological parameters for which the sex did not present a significant effect. The significance level was p ≤0.05. RESULTS: Significant effects were seen regarding the following: mean corpuscular volume (MCV), in which the verum group showed an increase (29.78 ± 52.95 fL) while the control group showed stability/reduction (-3.08 ± 46.36 fL) (p = 0.049); proportion of heterophils, in which the verum group showed a less marked increase (8.38 ± 12.53%) than that of the control group (18.00 ± 9.37%) (p = 0.010); lymphocyte concentration, in which the verum group showed less marked reduction (-4.39 ± 2.21 × 109 cells/L) than that of the control group (-1.56 ± 2.76 × 109 cells/L) (p = 0.001); and proportion of lymphocytes, in which the verum group showed a less marked reduction (-6.75 ± 10.35%) than that of the control group (-17.3 ± 8.73%) (p = 0.002). CONCLUSION: Comparison of samples collected before and during the reproductive period showed that, regardless of group allocation, there were differences in the effects on MCV, heterophils and lymphocytes. Treatment with Echinacea angustifolia and Avena sativa resulted in maintenance of lymphocyte levels in Magellanic penguins during the breeding period, thus aiding these birds' immunity.


Subject(s)
Echinacea , Homeopathy , Spheniscidae , Animals , Female , Male , Avena , Reproduction , Spheniscidae/physiology
10.
Homeopathy ; 112(2): 107-109, 2023 05.
Article in English | MEDLINE | ID: mdl-36055288

ABSTRACT

BACKGROUND: Homeopathic products (HP) have been proposed for the prevention of disease and as a complementary dietary additive in pig farming, with resulting improved performance and quality of life of the animals and with benefits for food safety. The aim of this study was to assess the addition of HP to pig feed and its effects on growth performance, dietary protein utilization, nutrient digestibility, meat quality, and economic feasibility. METHODS: A total of 80 male pigs, body weight 32.8±2.3kg, were allocated in a randomized design, with two treatments of 10 replications and four animals per experimental unit. Treatments were composed of a control diet (CD) or CD+HP (Finalvitaplus+Figotonus, 1.1kg/ton feed of each product). The outcome measures used were growth performance (body weight gain) and feed efficiency (body weight gain per unit of feed consumed), efficiency of dietary protein utilization (blood urea nitrogen), nutrient digestibility (apparent digestibility coefficient and apparent nutrient digestibility), meat quality (including pH, temperature, color, liquid loss by cooking and thawing, intramuscular fat and meat tenderness), and economic feasibility (cost of the diets). RESULTS: There was no effect (p >0.05) of treatments on growth performance of the pigs, though the group that received HP showed an 8.93% greater feed efficiency than the control group (p=0.077). The animals in the control group had a 14.37% higher blood urea nitrogen concentration in the finishing I phase (70-100kg body weight) compared with those fed HP (p=0.028), indicating lower protein utilization in the controls. There was comparative improvement in digestibility coefficient and in nutrient digestibility in pigs fed HP in the growing-finishing phase (p <0.05). There was no differential effect of treatments on meat quality or economic feasibility (p >0.05). CONCLUSION: The addition of HP to the diet of growing-finishing pigs produced some improvement in their dietary protein utilization, nutrient digestibility and feed efficiency, though it did not affect their growth performance, meat quality or economic feasibility.


Subject(s)
Homeopathy , Quality of Life , Animals , Male , Animal Feed/analysis , Body Weight , Diet/veterinary , Dietary Proteins/pharmacology , Digestion , Swine
11.
Homeopathy ; 112(1): 40-49, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35988582

ABSTRACT

INTRODUCTION: The use of mesenchymal stem cells (MSC) in cytotoxicity tests is an in-vitro alternative model for predicting initial doses. Homeopathic medicines may stimulate the immune system to combat a pathology effectively and have been used for over two centuries. Viscum album (VA) extracts are widely used in the treatment of cancer, due to their immunomodulatory, cytotoxic and pro-apoptotic properties. OBJECTIVE: This study aimed to evaluate the in-vitro growth kinetics of canine MSC in relation to cytotoxicity, cell differentiation and expression of pluripotentiality markers, using a VA preparation at the D1D2 (1×10-1, 1×10-2 potency (VAD1D2). METHODS: MSC were obtained from adipose tissue sampled from a healthy dog that was undergoing an elective veterinary procedure and with its owner's permission. The experiments were performed in three groups: MSC treated with VAD1D2 or diluent or untreated (control). The cytotoxicity was evaluated by MTT assay. The differentiation was induced in three lineages, and apoptotic cell labeling was performed by an Annexin-V test. RESULTS: At the concentration of 10 µL/mL of VA, the number of cells after in-vitro culture was maintained when compared with the control (untreated) group. A significant and gradual decrease in cell viability was recorded as VA concentrations increased. The apoptosis analysis showed that VA at 20 µL/mL presented absolute percentages of initial apoptosis twice as high as at 10 µL/mL, which was similar to the control (untreated group). CONCLUSION: The results suggest that the use of efficient methods to assess the in-vitro cytotoxicity of VA-based homeopathic medicines using MSC lineages may predict the potential action at different concentrations. These findings demonstrated that VAD1D2 interferes with canine MSC growth kinetics.


Subject(s)
Homeopathy , Mesenchymal Stem Cells , Viscum album , Animals , Dogs , Plant Extracts/pharmacology , Kinetics
12.
Int Wound J ; 20(7): 2855-2868, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36851877

ABSTRACT

Pressure ulcers often become chronic wounds that are difficult to treat and that tend to recur after healing. In China, convincing data from randomised trials have demonstrated that the pharmaceutical preparations of Periplaneta americana (KangFuXin Liquid, KFX) have a significant efficacy for pressure ulcers. To provide more reference to the clinicians and experts, we conducted a meta-analysis based on the existing randomised controlled trials (RCTs). We searched the RCTs about KFX for the treatment of pressure ulcers published up to July 2022 in major English and Chinese databases with no language restriction, including PubMed, EMBASE, Web of Science (WOS), Cochrane Central Register of Controlled Trials (CENTRAL), China Network Knowledge Infrastructure (CNKI), Chinese Biomedicine (CBM), Chinese Scientific Journals Database (VIP), and WanFang database. Cochrane Handbook guidelines were used to assess the risk of bias and to evaluate the methodological quality of included RCTs. Estimates of the intervention's effects are expressed as the risk ratio (RR) (95% CI) for binary outcomes and mean difference or standardised mean difference (95% CI) for continuous outcomes. We applied fixed or random effects models, and all analyses were performed using Review Manager version 5.4 and Stata/SE version 12.0. We included 22 studies with a total of 1575 participants. Compared with controls, KFX combined with basic wound care or KFX combined with basic wound care and another topical drug or physical treatment significantly increase clinical efficacy (RR: 1.17; 95% CI, 1.06-1.28; P = 0.001; I2  = 81%) and shorten the complete healing time (MD = -5.11; 95% CI [-8.19, -2.02]; P = 0.001) for pressure ulcers. Subgroup analysis showed a significant difference in the total clinical effect rate between KFX combined with basic wound care and controls. (n = 1018, RR 1.21, 95% CI [1.07, 1.36], I2  = 82%, P = 0.003). No difference was found in the total clinical effective rate between patients using KFX combined with basic wound care and another topical drug or physical treatment with controls (KFX combined with basic wound care and topical physical treatment: n = 267, RR 1.15, 95% CI [0.86, 1.52], I2  = 87%, P = 0.34; KFX combined with basic wound care and topical drug: n = 290, RR 1.05, 95% CI [0.80, 1.37], I2  = 86%, P = 0.71). Based on treatment duration, subgroup analysis indicated that increasing treatment duration increased the total clinical effective rate when treatment duration was not long. (treatment duration: 14 days: n = 158, OR 5.48, 95% CI [1.47, 20.43], I2  = 0%, P = 0.01; 21 days: n = 132, OR 5.93, 95% CI [1.86, 18.91], I2  = 65%, P = 0.003). When treatment duration was 28 days or 30 days, the results showed that there was no significant difference in total clinical effective rate between interventions and controls (treatment duration: 28 days: n = 107, OR 3.04, 95% CI [0.25, 37.32], I2  = 50%, P = 0.38; 30 days: n = 256, OR 0.58, 95% CI [0.11, 3.15], I2  = 65%, P = 0.53). No data on side effects were reported in any of the 22 studies. The conclusion is that the combination of KFX and basic wound care is effective in increasing the total clinical effectiveness and shortening the complete healing time of pressure ulcers.


Subject(s)
Materia Medica , Periplaneta , Pressure Ulcer , Humans , Animals , Pressure Ulcer/drug therapy , Treatment Outcome
13.
Turk J Med Sci ; 53(2): 463-474, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37476882

ABSTRACT

BACKGROUND: Renal ischemia-reperfusion (IR) related acute kidney injury (AKI) is an important health problem and has not yet been fully treated. Tarantula cubensis extract (TCE) is a homeopathic drug that has antiinflammatory and antioxidant effects. This study aimed to investigate the effects of TCE on renal ischemia-reperfusion injury in rats. METHODS: This study was carried out on 48 Spraque-Dawley male rats, which were divided into six groups. The first, second, and third groups were control, sham, and IR groups, respectively. Group four received IR and 0.2 mL of 96% ethanol. Group five and six received ischemia and reperfusion and TCE 0.01 and 0.1 mg per rat (which correspond to approximately 0.04 mg/kg, and 0.4 mg/kg), respectively. Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1ß), total antioxidant status (TAS), and total oxidant status (TOS) levels in renal tissue were measured by enzyme-linked immunosorbent assay (ELISA). Oxidative stress index (OSI) was obtained by proportioning TAS and TOS. Superoxide dismutase (SOD), myeloperoxidase (MPO) activities, and malondialdehyde (MDA) levels were determined by manual spectrophotometric methods. The histopathological changes were evaluated via hematoxylineosin and immunohistochemical staining. RESULTS: In IR group, renal tissue TNF-α and IL-1ß levels were significantly higher than control group (p < 0.0001 for both), and low(p < 0.0001 for both) and high dose (p < 0.0001 for both) TCE administration decreased these markers. Low and high doses of TCE decreased OSI values compared with IR group (p = 0.04 and p = 0.001 respectively). Although TCE decreased MDA levels, it was not statistically significant. MPO levels significantly decreased. In addition, TCE has been found to prevent hemorrhage, cast formation, and dilatation caused by IR in renal tissues stained with hematoxylin-eosin. And also, the most intense nuclear factor kappa B (NFκB) and caspase-3 immunopositivity found in IR group was decreased in both of the TCE groups. DISCUSSION: Although TCE showed a protective effect by inhibiting inflammation against IR damage in renal tissues, there was no clear effect on oxidative stress. Larger and more detailed studies are needed to clarify the issue.


Subject(s)
Acute Kidney Injury , Reperfusion Injury , Rats , Male , Animals , Tumor Necrosis Factor-alpha/metabolism , Kidney , Reperfusion Injury/pathology , Acute Kidney Injury/drug therapy , Oxidative Stress , Antioxidants/metabolism , Ischemia
14.
Hum Reprod ; 37(6): 1161-1174, 2022 05 30.
Article in English | MEDLINE | ID: mdl-35451013

ABSTRACT

STUDY QUESTION: Does addition of choriogonadotropin beta (recombinant CG beta) to follitropin delta increase the number of good-quality blastocysts following ovarian stimulation in a long GnRH agonist protocol? SUMMARY ANSWER: At the doses investigated, the addition of CG beta reduced the number of intermediate follicles and related down-stream parameters including the number of oocytes and blastocysts. WHAT IS KNOWN ALREADY: CG beta is a novel recombinant hCG (rhCG) molecule expressed by a human cell line (PER.C6®) and has a different glycosylation profile compared to urinary hCG or rhCG derived from a Chinese Hamster Ovary (CHO) cell line. In the first-in-human trial, the CG beta pharmacokinetics were similar between men and women. In women, the AUC and the peak serum concentration (Cmax) increased approximately dose proportionally following single and multiple daily doses. In men, a single dose of CG beta provided higher exposure with a longer half-life and proportionately higher testosterone production than CHO cell-derived rhCG. STUDY DESIGN, SIZE, DURATION: This placebo-controlled, double-blind, randomized trial (RAINBOW) was conducted in five European countries to explore the efficacy and safety of CG beta as add-on treatment to follitropin delta in women undergoing ovarian stimulation in a long GnRH agonist protocol. Randomization was stratified by centre and age (30-37 and 38-42 years). The primary endpoint was the number of good-quality blastocysts (Grade 3 BB or higher). Subjects were randomized to receive either placebo or 1, 2, 4, 8 or 12 µg CG beta added to the daily individualized follitropin delta dose during ovarian stimulation. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 620 women (30-42 years) with anti-Müllerian hormone (AMH) levels between 5 and 35 pmol/l were randomized in equal proportions to the six treatment groups and 619 subjects started treatment. All 619 subjects were treated with an individualized dose of follitropin delta determined based on AMH (Elecsys AMH Plus Immunoassay) and body weight. Triggering with rhCG was performed when 3 follicles were ≥17 mm but no more than 25 follicles ≥12 mm were reached. MAIN RESULTS AND THE ROLE OF CHANCE: The demographic characteristics were comparable between the six treatment groups and the overall mean age, body weight and AMH were 35.6 ± 3.3 years, 65.3 ± 10.7 kg and 15.3 ± 7.0 pmol/l, respectively. The incidence of cycle cancellation (range 0-2.9%), total follitropin delta dose (mean 112 µg) and duration of stimulation (mean 10 days) were similar across the groups. At stimulation Day 6, the number and size of follicles was similar between the treatment groups, whereas at the end-of-stimulation dose-related decrease of the intermediate follicles between 12 and 17 mm was observed in comparison to the placebo group. In contrast, the number of follicles ≥17 mm was similar between the CG beta dose groups and the placebo group. A reduced number of intermediate follicles (12 to 17 mm) and fewer oocytes (mean range 9.7 to 11.2) were observed for all doses of CG beta compared to the follitropin delta only group (mean 12.5). The mean number of good-quality blastocysts was 3.3 in the follitropin delta group and ranged between 2.1 and 3.0 across the CG beta groups. The incidence of transfer cancellation was higher in the 4, 8 and 12 µg group, mostly as no blastocyst was available for transfer. In the group receiving only follitropin delta, the ongoing pregnancy rate (10-11 weeks after transfer) was 43% per started cycle versus 28-39% in CG beta groups and 49% per transfer versus 38-50% in the CG beta groups. There was no apparent effect of CG beta on the incidence of adverse events, which was 48.1% in the placebo group and 39.6-52.3% in the CG beta dose groups. In line with the number of collected oocytes, the overall ovarian hyperstimulation syndrome incidence remained lower following follitropin delta with CG beta (2.0-10.3%) compared with follitropin delta only treatment (11.5%). Regardless of the dose, CG beta was safe and well-tolerated with low risk of immunogenicity. LIMITATIONS, REASONS FOR CAUTION: The effect of the unique glycosylation of CG beta and its associated potency implications in women were not known prior to this trial. Further studies will be needed to evaluate optimal doses of CG beta for this and/or different indications. WIDER IMPLICATIONS OF THE FINDINGS: The high ongoing pregnancy rate in the follitropin delta group supports the use of individualized follitropin delta dosing in a long GnRH agonist protocol. The addition of CG beta reduced the presence of intermediate follicles with the investigated doses and negatively affected all down-stream parameters. Further clinical research will be needed to assess the optimal dose of CG beta in the optimal ratio to follitropin delta to develop this novel combination product containing both FSH and LH activity for ovarian stimulation. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Ferring Pharmaceuticals, Copenhagen, Denmark. B.M. and P.L. are employees of Ferring Pharmaceuticals. M.F.S., H.V., C.Y.A., M.F., C.B., A.P. and Y.K. have received institutional clinical trial fees from Ferring Pharmaceuticals. C.B. has received payments for lectures from Organon, Ferring Pharmaceuticals, Merck A/S and Abbott. M.F.S. has received payment for lectures from Ferring Pharmaceuticals. Y.K. has received payment for lectures from Merck and travel support from Gedeon Richter. H.V. has received consulting fees from Oxo and Obseva and travel support from Gedeon Richter, Ferring Pharmaceuticals and Merck. C.Y.A. has received payment for lectures from IBSA, Switzerland. M.F and C.Y.A. were reimbursed as members of the Data Monitoring Board in this trial. M.F. has an issued patent about unitary combination of FSH and hCG (EP1633389). TRIAL REGISTRATION NUMBER: 2017-003810-13 (EudraCT Number). TRIAL REGISTRATION DATE: 21 May 2018. DATE OF FIRST PATIENT'S ENROLMENT: 13 June 2018.


Subject(s)
Follicle Stimulating Hormone, Human , Ovulation Induction , Animals , Anti-Mullerian Hormone , Body Weight , CHO Cells , Chorionic Gonadotropin , Chorionic Gonadotropin, beta Subunit, Human , Cricetinae , Cricetulus , Female , Fertilization in Vitro/methods , Gonadotropin-Releasing Hormone , Humans , Ovulation Induction/methods , Pharmaceutical Preparations , Pregnancy , Pregnancy Rate , Randomized Controlled Trials as Topic , Recombinant Proteins
15.
Rev Endocr Metab Disord ; 23(6): 1275-1284, 2022 12.
Article in English | MEDLINE | ID: mdl-35999482

ABSTRACT

The pursuit of longevity, which during the Renaissance era was limited to longing for miraculous ways of rejuvenation, such as bathing in the fountain of youth, took a scientific turn in 1889 with the publication of Brown-Sequard's self-experiments with an extract of animal testes, which apparently improved his vitality, physical strength and cognition. This extract, marketed then as the "Elixir of Life", was sold for decades throughout Europe and North America. However, recent replication of Brown-Sequard's experiments demonstrated that such an extract only contains homeopathic concentrations of testosterone that are insufficient to exert any biological effect. Thus, the birth of Andrology began with a placebo effect. Over the past few decades, the quest for compounds that might lead to rejuvenation has regained traction, with testosterone being at the forefront. Though clinical practice guidelines advocate testosterone therapy in men with organic hypogonadism-the only indication approved by the Food and Drug Administration-testosterone continues to be marketed as a wonder drug with rejuvenating effects on sexual function, vitality, and a host of other unproven benefits. Additionally, the epidemic of obesity and diabetes, conditions associated with low testosterone, has further brought testosterone into the limelight. Although the number of testosterone prescriptions written have increased several-fold in the past two decades, carefully conducted randomized trials suggest modest benefits of testosterone therapy. At the same time, safety concerns, particularly in older men, remain valid.


Subject(s)
Hypogonadism , Testosterone , Male , Animals , Humans , Testosterone/therapeutic use , Medicalization , Hypogonadism/drug therapy , Testis , Obesity/complications
16.
Horm Behav ; 144: 105201, 2022 08.
Article in English | MEDLINE | ID: mdl-35653830

ABSTRACT

Genistein possesses estrogenic activity and has been considered a potential replacement for estrogen replacement therapy after menopause. In the current study, we investigated the neuroprotective effects of dietary genistein at varied lengths of estrogen deprivation in middle-aged ovariectomized Sprague-Dawley rats under ischemic conditions. Two weeks of treatment with dietary genistein at 42 mg/kg but not 17ß-estradiol implants improved cognitive flexibility (Morris water maze test) after short-term estrogen deprivation (2 weeks) but not long-term estrogen deprivation (12 weeks). 17ß-estradiol implants but not dietary genistein improved locomotor asymmetry (cylinder test) after long-term but not short-term estrogen deprivation. Dietary genistein but not 17ß-estradiol implant improved early phase motor learning (rotarod test) after long-term estrogen deprivation. Neither 17ß-estradiol implant nor dietary genistein reduced infarct size after either short-term or long-term estrogen deprivation. Genistein, however, reduced ionized calcium-binding adaptor molecule-1 (Iba1) expression, a marker of brain inflammation, at the ipsilateral side of stroke injury after short-term but not long-term estrogen deprivation. This study suggests that the neuroprotective effects of dietary genistein on motor and cognitive functions are distinctly influenced by the length of estrogen deprivation following focal ischemia. SIGNIFICANCE: There is an increasing postmenopausal population opting for homeopathic medicines for the management of menopausal symptoms due to the perceived distrust in estrogen use as hormone replacement. Basic and clinical studies support the notion that early, but not delayed, hormone replacement after menopause is beneficial. Furthermore, evidence suggests that delaying hormone replacement augments the detrimental, rather than the beneficial effects of estrogens. Because of the active consideration of soy isoflavones including genistein as alternatives to estrogen replacement, it is necessary to understand the ramifications of soy isoflavones use when their administration is begun at various times after menopause.


Subject(s)
Genistein , Neuroprotective Agents , Animals , Cognition , Estradiol/pharmacology , Estradiol/therapeutic use , Estrogens/metabolism , Estrogens/pharmacology , Female , Genistein/pharmacology , Humans , Ischemia/drug therapy , Ovariectomy , Rats , Rats, Sprague-Dawley
17.
BMC Vet Res ; 18(1): 273, 2022 Jul 13.
Article in English | MEDLINE | ID: mdl-35831890

ABSTRACT

BACKGROUND: Mastitis is one of the major diseases in dairy cattle, as it causes great economic losses to producers due to the reduction of milk production and changes in the quality of the product. The disease is mainly caused by bacteria of the genus Staphylococcus spp., these microorganisms can express various virulence factors, such as biofilms for example. In herds with organic management, producers and technicians use unconventional ways to treat and control the disease, such as homeopathy. However, it is not known if this type of treatment is able to control pathogenic bacteria such as those of the genus Staphylococcus, of relevance to animal and human health. Thus, the objective of this study was to investigate the production of biofilm in vitro and its genes by Staphylococcus spp. isolated in the milk of cows treated with homeopathy, as well as the persistence of microorganisms in animals. METHODS: Ninety-nine isolates of Staphylococcus spp. from cows treated and not treated with homeopathy were identified by internal transcribed space-polymerase chain reaction and investigated for the presence of the icaABCD, bap, aap, atlE, and bhp genes and in vitro biofilm production using the adhesion method on polystyrene plates. The enzyme restriction profile was determined by Pulsed-Field Gel Electrophoresis. Clusters of S. aureus and S. epidermidis with three or more isolates had an isolate selected for Multilocus Sequence Typing. RESULTS: The frequency of S. aureus isolations was similar in treated and untreated cows, while 71.4% of the coagulase-negative identified were isolated in cows treated with homeopathy. The distribution of the operon ica genes was similar in animals with and without treatment, except for the icaD gene, more frequent in treated cows. Production of biofilm was associated with presence of one or more genes from the icaADBC operon. S. aureus revealed a greater diversity and greater dissemination in cows treated and not treated with homeopathy. Sequence Types ST1, ST5, and ST126 were identified in S. aureus. CONCLUSIONS: The presence of biofilm-associated genes and the in vitro production of biofilms, combined with the persistence of clonal profiles of Staphylococcus spp. demonstrate other forms of control for bovine mastitis should be researched for organic production herds.


Subject(s)
Cattle Diseases , Homeopathy , Mastitis, Bovine , Staphylococcal Infections , Animals , Biofilms , Cattle , Female , Homeopathy/veterinary , Humans , Mastitis, Bovine/microbiology , Mastitis, Bovine/therapy , Milk/microbiology , Staphylococcal Infections/microbiology , Staphylococcal Infections/veterinary , Staphylococcus/genetics , Staphylococcus aureus/genetics
18.
Regul Toxicol Pharmacol ; 134: 105215, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35842056

ABSTRACT

The present successor article comprises more than 180 substances representing a continuative compilation of toxicologically evaluated starting materials prompted by the wide use and high number of homeopathic and anthroposophic medicinal products (HMP) on the market together with the broad spectrum of active substances of botanical, mineral, chemical or animal origin contained therein, and by the equally important requirement of applying adequate safety principles as with conventional human medicinal products in line with the European regulatory framework. The February 2019 issue of the Regulatory Toxicology and Pharmacology journal includes the antecedent article bearing the same title and entailing safety evaluations of more than 170 raw materials processed in HMP. This part 2 article highlights scientific evaluation following recognized methods used in toxicology with a view to drug-regulatory authority's assessment principles and practice in the context of HMP, and offers useful systematic, scientifically substantiated and simultaneously pragmatic approaches in differentiated HMP risk assessment. As a unique feature, both articles provide the most extensive publicly available systematic compilation of a considerable number of substances processed in HMP as a transparent resource for applicants, pharmaceutical manufacturers, the scientific community and healthcare authorities to actively support regulatory decision making in practice.


Subject(s)
Homeopathy , Animals , Humans , Risk Assessment/methods
19.
Lett Appl Microbiol ; 74(4): 564-576, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34958703

ABSTRACT

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.


Subject(s)
Candidiasis, Vulvovaginal , Materia Medica , Animals , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida albicans , Candidiasis, Vulvovaginal/drug therapy , Candidiasis, Vulvovaginal/microbiology , Female , Fluconazole/pharmacology , Fluconazole/therapeutic use , Materia Medica/pharmacology , Materia Medica/therapeutic use , Mice
20.
Homeopathy ; 111(4): 271-277, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35259770

ABSTRACT

BACKGROUND: Myiasis by Cochliomyia hominivorax (Diptera: Calliphoridae) is a serious problem in animal health in tropical and sub-tropical regions. Ointment-type preparations are a good option of formulation in cases of myiasis in farm and pet animals. Sulphur and Pyrogenium have already shown in-vitro efficacy on C. hominivorax. This article describes an in-vitro experiment to test the inhibition of development from exposing larvae of C. hominivorax to two homeopathic ointments (prepared individually with Sulphur or Pyrogenium). METHODS: The homeopathic ointments were produced by mixing sterile lanolin, tocopherol and homeopathic medicine on a hydroalcoholic basis according to the Brazilian Homeopathic Pharmacopoeia. Larvae were obtained from naturally occurring myiases in sheep (wild larvae) or from a laboratory colony. The test consisted of exposing a group of 10 third-stage C. hominivorax wild larvae in contact with Sulphur or Pyrogenium ointment, or a group of 15 laboratory-propagated larvae in contact with the alcoholic vehicle of the ointment or homeopathic medicines prepared in sterile water (Sulphur or Pyrogenium), and observing the effect on the development, longevity and fertility of the blow-fly specimens. RESULTS: The C. hominivorax larval inhibition rate was 90.0% for the Sulphur ointment group and was 86.0% for the Pyrogenium ointment group. The non-alcoholic vehicle and the alcoholic vehicle inhibited the development of 24.0% and 22.08% of the larvae respectively. Sulphur prepared in sterile water inhibited the development of 74.67% and Pyrogenium in sterile water inhibited 73.33% of larvae. Specimens that survived contact with homeopathic ointments had their longevity decreased and did not reproduce. CONCLUSION: Ointments of Sulphur or Pyrogenium were able to inhibit the development of C. hominivorax larvae. The ointment vehicle was harmless.


Subject(s)
Diptera , Homeopathy , Materia Medica , Myiasis , Animals , Sheep , Calliphoridae , Larva , Ointments/pharmacology , Myiasis/veterinary , Sulfur/pharmacology , Materia Medica/pharmacology , Water
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