Evaluation of uterine antioxidants in bitches suffering from cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia-pyometra complex (CEH-P) is a common disease in sexually mature bitches. Disease progression leads to oxidative stress, resulting in the depletion of uterine antioxidants and lipid peroxidation of associated cells, which further aggravates the condition. The concentration of antioxidant enzymes, the level of lipid peroxidation within the uterine tissue, and its reflection in the serum and urine need to be elucidated. The aim of this study was to analyze the concentration of antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and the lipid peroxidation marker malonaldehyde (MDA) in three types of samples, i.e., serum, urine, and uterine tissue. For this purpose, 58 pyometra-affected and 44 healthy bitches were included in the present study. All animals underwent ovariohysterectomy (OVH). Our data indicated highly significant difference (p<0.01) in the antioxidant concentrations of uterine, serum and urine samples. Furthermore, there was a highly significant (p<0.01) difference in the serum levels of ferric reducing antioxidant power (FRAP) and free radical scavenging activity (FRSA) indicated poor capacity to overcome oxidative stress in the CEH-Pyometra condition. We showed that CEH-P induces oxidative stress, which further depletes the antioxidant enzyme reserves in the uterus. Thus, the weak antioxidant defence predisposes to uterine damage and disease progression. The simultaneous depletion of antioxidants and an increase in lipid peroxidation in the serum and urine may also act as early indicators of uterine pathology.

Theileria annulata Induced Bilateral Ocular Signs in Cattle and Its Successful Therapeutic Management: A Case Report.

Bovine tropical theileriosis is one of the potentially fatal disease of dairy cattle, which is caused by hemoparasite Theleria annulata. About seven years old cross-bred cow was presented with complaint of pyrexia, inappetance, lacrimation and ocular swelling since last 5 days. The clinical examination showed elevated rectal temperature (39.4 °C), mild enlarged pre-scapular lymph nodes, bilateral bulging of temporal fossa, protruded pale and icteric conjunctivae of the eyes with lacrimation and presence of ticks on body. The case was suspected for haemoprotozoan disease. Blood and serum sample were collected for hematological, blood smear examination and molecular examination (PCR), and biochemical analysis respectively. Microscopic examination of blood smear revealed intra-erythrocytic signet ring shaped periplasm of Theileria annulata. Hemato-biochemical examination revealed anemia, hypoproteinemia, hypoalbuminemia and jaundice. Further, PCR assay was done using T. annulata-specific primer pair, Cyto b1 gene targeting the amplicon of 312 bp showed specific band on Gel-electrophoresis. Therapeutic regimen was started with Buparvaquone @ 2.5 mg/kg body weight IM single dose followed by Oxytetracycline @ 10 mg/kg body weight IV in 500 ml of NS for 5 days and Prednisolone @ 0.25 mg/kg body weight IM for 3 days along with supportive therapy. The cattle well responded to the therapy and complete regression of ocular signs was observed within one week of treatment.

Indigenous chicken production system in different agro-ecology of Indian Himalayan Region: implication on food and economic security.

The indigenous chicken production system (ICPS) has several use values and ecosystem services. In the last few years, ICPS has been recognized for its possible contribution to household food security, income generation, wildlife protection, and bettering the women's lives. This study aimed to collect, for the first time, comprehensive information about ICPS in three different agro-ecologies (tropical, sub-tropical, and sub-temperate) of the Indian Himalayan Region (IHR) and its role in food and economic security of traditional communities. In this study region, ICPS is semi-extensive, providing homegrown feed and temporary night shelter. In sub-temperate agro-ecology, females owned non-significant (p = 0.170) more indigenous chicken flocks than males. Households in sub-temperate agro-ecologies had significantly (p ≤ 0.001) larger flock sizes and tropical livestock units (chicken-TLU). However, the livestock diversity index (LDI) was significantly higher (p ≤ 0.001) in tropical and subtropical agro-ecology. The households in the sub-temperate region highly (p ≤ 0.001) valued indigenous chicken because of its survivability and adaptability. In absolute numbers significant (p ≤ 0.001) higher numbers of adult birds died in past 1 year in sub-temperate agro-ecology. The mortality rate of adult birds in sub-temperate agro-ecology was 9%, and it was 14 and 15% in tropical and sub-tropical agro-ecologies, respectively. In sub-temperate agro-ecology, larger flock size translated into significantly higher (p ≤ 0.001) egg production and subsequently a significant (p ≤ 0.001) higher egg consumption per household per month. In sub-temperate agro-ecology, households' dietary diversity score was significantly (p ≤ 0.001) higher. Similarly, the average annual income from ICPS was significantly higher (p ≤ 0.001) in sub-temperate agro-ecology and accounted for 18% of household income. ICPS' marketing chain was relatively short in the sub-temperate region. In all agro-ecologies, indigenous chicken and egg demand was significantly higher (p ≤ 0.001) in the winter. ICPS litter is used as farmyard manure, enhancing ecological resilience. In all agro-ecologies, the three most frequently cited obstacles to extending the indigenous chicken production system are illnesses, predators, and a lack of chicks availability. ICPS contributes to food and nutritional security, economic stability, and ecological resilience in this hilly and fragile ecosystem. Even though the system is self-sustaining, management and health interventions can increase production and productivity.

Effect of some phytoconstituents on Fe2+/ascorbate induced lipid peroxidation.

Transition metals like iron and copper, present inside the body system play a key role in the production of reactive oxygen radicals. These free radicals, causative agents of lipid peroxidation, not only damage proteins and DNA but also gradually changes the cellular membrane structure and ultimately leads to the loss of function and integrity. Uncontrolled lipid peroxidation results in various age related diseases, malignancy, infective diseases and injuries. Antioxidants and other phytochemical constituents present in the various plants are known to protect cells from such reactive oxygen species (ROS)-mediated damages. Here, we evaluated the effect of certain phytoconstituents present in the well-known medicinal plants on ROS scavenging using rat liver homogenate. The basal lipid peroxidation was found to be 0.1625±0.0095 ngMDA/min/mg protein, which got induced to 0.7938±0.0478 ngMDA/min/mg protein in the presence of Fe2+/ascorbate system. In this context, acteoside, berberine, catechin, 3´5-dihydroxyflavone7-o-ß-D-galacturonide-4-o-ß-D-glucopyranoside (a flavonoid glycoside from cumin), silibin and tetrahydrocurcumin decreased both basal and Fe2+/ascorbate induced lipid peroxidation as determined by thiobarbituric acid reaction. On the other hand, agnuside, andrographolide, picroside-I, negunoside, oleanolic acid, and glycerrihizin, showed enhancement in both basal and induced lipid peroxidation. Phytoconstituents which have decreased both basal and Fe2+/ascorbate induced lipid peroxidation may act as defensive against the deadly effects of ROS, causative agents of lipid peroxidation and other diseases either alone or in combination with diet/nutritional supplements.

Nitrofuranyl Methyl Piperazines as New Anti-TB Agents: Identification, Validation, Medicinal Chemistry, and PK Studies.

Whole-cell screening of 20,000 drug-like small molecules led to the identification of nitrofuranyl methylpiperazines as potent anti-TB agents. In the present study, validation followed by medicinal chemistry has been used to explore the structure-activity relationship. Ten compounds demonstrated potent MIC in the range of 0.17-0.0072 µM against H37Rv Mycobacterium tuberculosis (MTB) and were further investigated against nonreplicating and resistant (Rif(R) and MDR) strains of MTB. These compounds were also tested for cytotoxicity. Among the 10 tested compounds, five showed submicromolar to nanomolar potency against nonreplicating and resistant (Rif(R) and MDR) strains of MTB along with a good safety index. Based on their overall in vitro profiles, the solubility and pharmacokinetic properties of five potent compounds were studied, and two analogues, 14f and 16g, were found to have comparatively better solubility than others tested and acceptable pharmacokinetic properties. This study presents the rediscovery of a nitrofuranyl class of compounds with improved aqueous solubility and acceptable oral PK properties, opening a new direction for further development.

Synthesis and Biological Evaluation of Polar Functionalities Containing Nitrodihydroimidazooxazoles as Anti-TB Agents.

Novel polar functionalities containing 6-nitro-2,3-dihydroimidazooxazole (NHIO) analogues were synthesized to produce a compound with enhanced solubility. Polar functionalities including sulfonyl, uridyl, and thiouridyl-bearing NHIO analogues were synthesized and evaluated against Mycobacterium tuberculosis (MTB) H37Rv. The aqueous solubility of compounds with MIC values ≤0.5 µg/mL were tested, and six compounds showed enhanced aqueous solubility. The best six compounds were further tested against resistant (Rif(R) and MDR) and dormant strains of MTB and tested for cytotoxicity in HepG2 cell line. Based on its overall in vitro characteristics and solubility profile, compound 6d was further shown to possess high microsomal stability, solubility under all tested biological conditions (PBS, SGF and SIF), and favorable oral in vivo pharmacokinetics and in vivo efficacy.

Femoropopliteal in-stent restenosis: current treatment strategies.

Nitinol self-expanding stents are increasingly used to treat symptomatic peripheral arterial disease. Despite reduction in procedural complications and rates of stent fracture, femoropopliteal in-stent restenosis (FP-ISR) remains a common and important clinical problem. Due to heterogenous patient and angiographic characteristics, treatment of FP-ISR continues to evolve. Multiple modalities have been evaluated including standard balloon angioplasty, cutting or scoring balloon angioplasty, repeat stenting (nitinol stent vs. stent-graft vs. drug eluting stent), excisional or laser atherectomy, drug coated balloon angioplasty, and atherectomy followed by drug coated balloon angioplasty. This review highlights the clinical evidence for the currently available modalities in the treatment of FP-ISR. Future studies should utilize uniform classification schemes and assess similar outcomes to help determine the optimal approach for endovascular treatment of FP-ISR.

Involvement of P-glycoprotein and CYP 3A4 in the enhancement of etoposide bioavailability by a piperine analogue.

Etoposide, a semi-synthetic derivative of podophyllotoxin, is widely used anticancer agent. Etoposide presents low bioavailability with wide inter-, and intra-patient variability after oral dosing. In an earlier study a piperine analogue, namely, 4-ethyl 5-(3, 4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1), was shown to cause 2.32-fold enhancement of the absolute bioavailability of co-dosed etoposide in mice. In the present investigation a mechanistic evaluation was undertaken using various in vitro and animal-derived models. In everted rat gut sac studies PA-1 enhanced mucosal uptake of the drug while it inhibited efflux of Rh-123, a P-glycoprotein substrate from serosal-to-mucosal direction. In a single pass in situ perfusion experiment PA-1 significantly reduced the intestinal exsorption rate, exsorption clearance and the total plasma clearance of etoposide. On the other hand PA-1 did not alter the passive diffusion pattern of the drug in PAMPA assay. PA-1 was inhibitory to NADPH-assisted deethylation and demethylation reactions catalyzed by erythromycin N-demethylase, 7-methoxycoumarin-O-demethylase (MOCD) and ethoxyresorufin-O-deethylase (EROD). PA-1 was not cytotoxic to mucosal membrane and showed no adverse effect in acute toxicity determination. The results suggested that PA-1-mediated enhancement in the oral bioavailability of etoposide could possibly be due to its ability to modify P-gp/CYP 3A4 mediated drug disposition mechanisms.

Anti-histaminic potential of fractions from Hedranthera barteri [(Hook F.) Pichon] root in laboratory rodents.

Hedranthera barteri, anti-inflammatory activity, anti-nociceptive activity, anti-histaminic activityL. (HB) is used in the treatment of painful conditions and oedema amongst its folkloric use. The hexane and ethyl acetate fractions of the root of H. barteri were investigated for anti-nociceptive and antiinflammatory properties and probable mechanism of action. Hot plate, tail flick, formalin-induced oedema and acetic acidinduced writhing tests were employed to investigate the anti-nociceptive activity while the anti-inflammatory activity was investigated using carrageenan-induced paw oedema. Anti-histaminic potential of HB root extracts on the rat peritoneal mast cells (RPMCs) was explored through pectrofluorometric method. The root was screened for its phytochemical components. The HB root contains alkaloids,cardenolides and saponins. HXHBR exhibited higher anti-inflammatory potentials (P <0.001). HXHBR dose-dependently (P <0.01) reduced the histamine release from the rat peritoneal mast cells which is comparable with a standard anti-histaminic drug, ketotifen. These results showed that EAHBR and HXHBR possess anti-nociceptive and anti-inflammatory activities, and suggested its mechanism of action through the inhibition of histamine, an inflammatory mediator, usually released during the early phase of allergic responses and chronic phase of inflammatory pain. Flavonoids, alkaloids and/or saponins present in HB root may be responsible for its anti-nociceptive and anti-inflammatory properties.

Assessment of 3-D nasal airway morphology in Southeast Asian adults with obstructive sleep apnea using acoustic rhinometry.

The aim of the present study is to investigate nasal airway morphology in Asian adults with and without obstructive sleep apnea (OSA) using acoustic rhinometry (AR), principal components analysis (PCA), and 3-D finite-element analysis (FEA). One hundred eight adult Malays aged 18-65 years (mean ± SD, 33.2 ± 13.31) underwent clinical examination and limited channel polysomnography, providing 54 patients with OSA and 54 non-OSA controls. The mean minimal cross section area 1 (MCA1) and the mean minimal cross sectional area 2 (MCA2) were obtained from AR for all subjects and subjected to t tests. The OSA and control nasal airways were reconstructed in 3-D and subjected to PCA and FEA. The mean MCA1 and MCA2 using AR were found to be significantly smaller in the OSA group than in the control group (p < 0.001). Comparing the 3-D OSA and control nasal airways using PCA, the first two eigenvalues accounted for 94% of the total shape change, and statistical differences were found (p < 0.05). Similarly, comparing the nasal airways using FEA, the 3-D mean OSA nasal airway was significantly narrower in the OSA group compared to the control group. Specifically, decreases in size of approx. 10-22% were found in the nasal valve/head of inferior turbinate area. In conclusion, differences in nasal airway morphology are present when comparing patients with OSA to controls. These differences need to be recognized as they can improve our understanding of the etiological basis of obstructive sleep apnea and facilitate its subsequent management.

Sub-acute toxicity evaluation of an aqueous extract of Labisia pumila, a Malaysian herb.

Labisia pumila (Myrsinaceae), is a popular herb among the women in Malaysia known locally as "Kacip Fatimah". Recently many nutraceutical products containing the powdered or extracted parts of the plant have become available for women's health care. However no evaluation of the effect of the repeated dosing of any herbal product of this plant had been undertaken prior to a 28-day sub-acute study presented in this report. The results showed that a dose of 50mg/kg of an aqueous extract of L. pumila corresponded to no-adverse-effect-level (NOAEL), whereas higher doses were associated with some toxicity concerns.

In vivo genotoxicity evaluation of a plant based antiarthritic and anticancer therapeutic agent Boswelic acids in rodents.

The genotoxic potential of anti-inflammatory/anti-arthritic and anticancer plant based drug molecule Boswelic acids (BA) was studied by in vivo system. Systematic literature survey revealed that studies on the genotoxicity of BA are not available. Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-beta-boswelic acid are available and these studies were conducted in in vitro systems. The earlier general toxicity study of BA has been conducted by us, revealed it to be non toxic. The genotoxicity was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Six groups of animals, each comprised of five rats, were taken for each study. Group1-4 received BA at 125, 250, 500 and 1000 mg/kg p.o., respectively prepared as 2% gum acacia suspension, fifth group received a positive control cyclophosphamide (CP) 40 mg/kg p.o. or metronedazole (MTZ) 130 mg/kg p.o. or mercuric chloride (HgCl(2)) 0.864 mg/kg p.o. (as per the experiment requirement) whereas the sixth group kept as vehicle control. The results on the bases of the data obtained revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000 mg/kg. The positive controls used in different experiments showed highly significant abnormal cytogenetic changes in comparison to the control group.

Anti-allergic effects of herbal product from Allium cepa (bulb).

Allium cepa (Family Liliaceae) is a reputed Indian medicinal herb that is prescribed as an effective remedy for several ailments in the Ayurvedic system of medicine. The aim of this study was to evaluate its efficacy against various events responsible for Type I allergic reactions. A herbal fraction (ALC-02) from A. cepa (bulb) inhibited histamine release and attenuated intracellular calcium levels in Compound 48/80-induced rat peritoneal mast cells. It also prevented Compound 48/80-mediated systemic anaphylaxis while lowering histamine levels in plasma. ALC-02 suppressed carrageenan-induced rat paw edema. It inhibited eosinophil peroxidase activity and protein content in bronchoalveolar lavage fluid (BALF) of ovalbumin-challenged mice. In this experiment ALC-02 also caused a substantial reduction in lipid peroxidation in BALF/lung tissue and augmented superoxide dismutase activity in lung tissue. ALC-02 suppressed erythrocytic lysis caused by Triton X-100. A significant quenching of 1,1-diphenyl-2-picrylhydrazyl radical by ALC-02 was observed. The results have shown a promising anti-allergic profile of ALC-02 that could be attributed to its potential antihistaminic, anti-inflammatory, and antioxidant activities.

Dental arch morphology in south-east Asian adults with obstructive sleep apnoea: geometric morphometrics.

The association between dental arch morphology and the aetiology of obstructive sleep apnoea (OSA) is not clear. To compare dental arch morphology in 108 Asian adults with and without ''OSA, overnight'' hospital polysomnography was performed, and sleep reports were obtained for all subjects. Standardized digital photographs were also taken of the subjects' upper and lower study models. Using 25 homologous landmarks, mean OSA and control dental arch configurations were computed, and subjected to finite-element morphometry (FEM), t-tests and principal components analysis (PCA). Mean upper and lower OSA dental arch morphologies were statistically different from respective Control upper and lower arch morphologies (P < 0.05). FEM of the upper arch indicated that the mean OSA configuration was 7-11% narrower in the transverse plane in the incisor and canine regions when compared with the control configuration, and inter-landmark analysis (ILA) confirmed this finding. FEM for the lower arch indicated that the mean OSA configuration was 10-11% narrower in the antero-posterior plane in the pre-molar and molar regions, and confirmed by ILA. Using PCA, significant differences were also found between the two groups in the lower arch using the first two eigenvalues, which accounted for 90% of the total shape change (P < 0.001). Supporting their role as aetiological factors, size and shape differences in dental arch morphology are found in patients with OSA.

Craniofacial obesity in patients with obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) and obesity are serious, widespread public health issues. OBJECTIVE: To localize and quantify geometric morphometric differences in facial soft tissue morphology in adults with and without OSA. MATERIALS AND METHODS: Eighty adult Malays, consisting of 40 patients with OSA and 40 non-OSA controls, were studied. Both groups were evaluated by the attending physician and through ambulatory sleep studies. 3-D stereophotogrammetry was used to capture facial soft tissues of both groups. The 3-D mean OSA and control facial configurations were computed and subjected to principal components analysis (PCA) and finite-element morphometry (FEM). RESULTS: The body mass index was significantly greater for the OSA group (32.3 kg/m(2) compared to 24.8 kg/m(2), p < 0.001). The neck circumference was greater for the OSA group (42.7 cm compared to 37.1 cm, p < 0.001). Using PCA, significant differences were found in facial shape between the two groups using the first two principal components, which accounted for 50% of the total shape change (p < 0.05). Using FEM, these differences were localized in the bucco-submandibular regions of the face predominantly, indicating an increase in volume of 7-22% (p < 0.05) for the OSA group. CONCLUSION: Craniofacial obesity in the bucco-submandibular regions is associated with OSA and may provide valuable screening information for the identification of patients with undiagnosed OSA.

Anti-histaminic, anti-inflammatory and bronchorelaxant activities of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one.

An immunopharmacological profile of 2, 7-dimethyl-3-nitro-4H pyrido [1,2-a] pyrimidine-4-one (P-I) has been investigated using in vitro and in vivo models representing various features of Type I allergy. P-I prevented compound 48/80-mediated histamine release from rat peritoneal mast cells. A promising anti-inflammatory activity of P-I was evident in active paw anaphylaxis (mice) and carragenan-induced paw edema (rat). P-I inhibited eosonophil accumulation and eosinophil peroxidase activity in bronchoalveolar lavage fluid from ovalbumin challenged balb/c mice: in these animals blood levels of IL-5, and CD4+ T cells also remained attenuated. A promising bronchorelaxant effect of P-I was observed in histamine-contracted guinea pig tracheal chain via its antagonism to H1 receptor. These findings were compared with some known compounds (ketotifen, cetirizine and promethazine). The anti-histaminic, anti-inflammatory and bronchorelaxant activities of P-I has been discussed in context with its potential profile as an anti-allergic and anti-asthmatic agent.

Digital diagnostics: Three-dimensional modelling.

Three-dimensional imaging techniques, such as computed tomograms (CT), structured light, and stereophotogrammetry, can be used to capture three-dimensional coordinate data, but comprehensive analysis is required to transform these techniques into powerful diagnostic tools. The object of this review is to highlight analytical functionality using software developed to study three-dimensional digital imaging and communications in medicine (DICOM) based digital data for diagnosis, planning of treatment, and evaluation of craniofacial changes. My specific aim was to apply three-dimensional software routines using geometric morphometrics or conventional measurements. These routines rely on robust algorithms to construct mean objects by manipulating the three-dimensional x, y, and z coordinates of all the objects' vertices. Conventional measurements and statistical tests can then be applied to the changes in the vertices, say, before and after treatment. Using graphical and geometric morphometric techniques such as finite-element analysis and principal components analysis, clinical craniofacial modelling can be used for the localisation and quantification of soft and hard tissue changes; diagnostic modelling can be undertaken for planning of treatment, and data-driven predictive modelling can be undertaken for the planning of many procedures based on the surgeon's own experience, patients, and resources. Three-dimensional modelling of digital data may therefore have added value for clinical diagnosis, and planning and assessment of treatment, including audit.