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1.
Open Vet J ; 14(1): 144-153, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38633157

RESUMO

Background: A commercially significant species in the aquaculture sector globally, particularly in Egypt, is Litopenaeus vannamei. Aim: The experiment's objective was to ascertain how Sanolife PRO-F impacted the growth, water quality, immunological response, and intestinal morphometry of L. vannamei. Methods: In the current investigation, which lasted 12 weeks, Sanolife PRO-F was administered to shrimp post-larvae at diet doses of 0 (control), 1 (group one), 2 (group two), and 3 (group three) g/kg diet, respectively. Each experimental group had three repetitions. Results: In the current study, shrimp fed on probiotic-treated diets showed a considerable improvement in growth performance measures and survival rate, and the nonspecific immune response was also enhanced. Shrimp fed probiotic diets had longer and more intestinal villi overall. Shrimp fed on the G2 and G3 diets showed no appreciable differences in growth or intestinal morphology. With the G2 and G3 diet, the water had lower concentrations of nitrite and ammonia. Conclusion: The study's findings indicate that Sanolife PRO-F treatment at 2-3 g/kg feed promotes the growth of shrimp, immunological response, gut health and function, and water quality.


Assuntos
Bacillus licheniformis , Bacillus pumilus , Penaeidae , Probióticos , Animais , Bacillus subtilis , Qualidade da Água , Imunidade Inata , Penaeidae/fisiologia , Probióticos/farmacologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-38623979

RESUMO

BACKGROUND: Due to its systemic toxicity, traditional chemotherapy of tumors is being taken into consideration. Herbal therapy, containing phytochemical polyphenol derivatives such as Curcumin (Cur), Ginger (Gin), Cloves (Clov) and Amygdaline (Amyg), is one of the numerous complementary and alternative approaches as an anti-cancer therapy and holds great promise for cancer chemo-prevention with fewer side effects. AIM: The current study was designated to assess anti-tumoral immunity and anti-cancer and chemo-preventive effectiveness of herbal extracts of Cur, Ginger, Clov and Amyg in Ehrlich Ascites Carcinoma (EAC)-challenging mice. METHODS: Chemo-preventive efficacy of herbal extracts of Cur, Gin, Clov and Amyg were analyzed in vivo by examination of the apoptosis rate of EAC tumor cells by flow cytometry. The total numbers of EAC cells, splenocytes counts and leucocytes count with their differentials relative % in peripheral blood (PB) of EACchallenging mice were investigated. RESULTS: EAC-challenging mice treated with herbal extracts of Cur, Gin, Clov and Amyg showed a marked decline in EAC tumor cell count and a noticeable increase in apoptosis rate of EAC tumor cells, a remarkable decrease in serum level of cancer antigen 125 (CA-125) with an obvious increase in the number of splenocytes comparing to that in EAC-challenging mice treated with PBS alone. Moreover, the data indicated an insignificant change in the total leucocytes count and their differentials relative % of eosinophil, neutrophils, monocytes and lymphocytes in EAC-challenging mice treated with Cur and Amyg, but these parameters were markedly increased in EAC-challenging mice injected with Gin and Clov compared to that in EAC-challenging mice treated with PBS alone. CONCLUSION: To conclude, the herbal extracts of Cur, Gin, Clov and Amyg may have anti-tumoral immunity and anti-cancer potency and potential to reduce the resistance to cancer conventional chemotherapy and exert cancer chemo-protective approaches with low adverse effects. Further research is necessary to determine the regimen's toxicity on various tissues and organs and to connect the diagnostic and therapeutic approaches used in the regimen's biomedical use.

3.
Heliyon ; 10(6): e27021, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38496835

RESUMO

Renewable energy sources have immense potential for enhancing environmental sustainability; however, addressing their intermittency and irregularity is vital for optimizing economic benefits within microgrids. Integrating renewable energy systems with energy storage presents a promising solution. This study introduces an innovative energy management system designed for hybrid renewable power stations, incorporating battery energy storage systems and diesel generators. By accounting for battery degradation costs associated with charge depth and lifespan, the study transforms long-term battery expenses into real-time operational costs. The optimization problem is formulated as a mixed integer linear programming framework with the objectives of minimizing operating costs, battery degradation costs, and pollutant gas emissions. Through diverse case studies reflecting various market profiles. The proposed approach demonstrates reductions in overall system costs.

4.
JCI Insight ; 9(6)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516887

RESUMO

Silver-Russell syndrome (SRS) is a heterogeneous disorder characterized by intrauterine and postnatal growth retardation. HMGA2 variants are a rare cause of SRS and its functional role in human linear growth is unclear. Patients with suspected SRS negative for 11p15LOM/mUPD7 underwent whole-exome and/or targeted-genome sequencing. Mutant HMGA2 protein expression and nuclear localization were assessed. Two Hmga2-knockin mouse models were generated. Five clinical SRS patients harbored HMGA2 variants with differing functional impacts: 2 stop-gain nonsense variants (c.49G>T, c.52C>T), c.166A>G missense variant, and 2 frameshift variants (c.144delC, c.145delA) leading to an identical, extended-length protein. Phenotypic features were highly variable. Nuclear localization was reduced/absent for all variants except c.166A>G. Homozygous knockin mice recapitulating the c.166A>G variant (Hmga2K56E) exhibited a growth-restricted phenotype. An Hmga2Ter76-knockin mouse model lacked detectable full-length Hmga2 protein, similarly to patient 3 and 5 variants. These mice were infertile, with a pygmy phenotype. We report a heterogeneous group of individuals with SRS harboring variants in HMGA2 and describe the first Hmga2 missense knockin mouse model (Hmga2K56E) to our knowledge causing a growth-restricted phenotype. In patients with clinical features of SRS but negative genetic screening, HMGA2 should be included in next-generation sequencing testing approaches.


Assuntos
Proteína HMGA2 , Síndrome de Silver-Russell , Animais , Humanos , Camundongos , Sequência de Bases , Transtornos do Crescimento/genética , Proteína HMGA2/genética , Fenótipo , Síndrome de Silver-Russell/genética , Síndrome de Silver-Russell/diagnóstico
5.
Cardiol Rev ; 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299806

RESUMO

This study aims to compare the effectiveness of leadless pacemakers (LPs) and transvenous pacemakers and to examine the safety of both methods. We included patients undergoing single-chamber pacemaker implantation, either LP or TVP. Our outcomes were successful implantation rate, major complication, vascular injury, tamponade, and pneumothorax. We performed a double-arm analysis comparing LP versus TVP, with risk ratio (RR) and 95% confidence interval. A total of 10 studies were included in this meta-analysis. Regarding efficacy endpoints, RR revealed no significant difference between the LP and transvenous pacemaker groups in terms of successful rate of implantation (RR = 1.00; P = 0.77). Regarding safety outcomes, LP experienced lower incidence of major complications (RR = 0.47; P = 0.01), infection (RR = 0.24; P = 0.001), and tamponade (RR = 0.36; P = 0.01). There was no significant difference between both groups regarding pneumothorax (RR = 0.35; P = 0.22) and vascular injury (RR = 1.55; P = 0.25). The study findings suggest that both LPs and TVPs have similar effectiveness. Moreover, the incidences of pneumothorax, vascular injuries, and major complications were found to be comparable between the 2 methods. However, LPs were found to have lower rates of infection and tamponade.

6.
Environ Toxicol ; 39(1): 388-397, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37782692

RESUMO

Although curcumin possesses anti-inflammatory, antioxidant, and cytoprotective qualities, its low absorption limits its medicinal uses. Before examining how curcumin influenced rats' liver fibrosis when thioacetamide (TAA) was produced, the current study employed nanoparticles (NPs) to improve curcumin bioavailability. Sixty mature rats were separated into six groups (Group 1, control; Group 2, curcumin; Group 3, curcumin nanoparticles; Group 4, TAA; Group 5, TAA + curcumin; Group 6, TAA + curcumin NPs). TAA administration caused considerable increases in serum liver enzymes associated with a remarkable depletion in the levels of albumin and total protein relative to the control. In addition, a significant elevation in malonaldehyde (MDA) level with a significant depletion in the antioxidant enzymes activity was detected. Also, TAA had a significant effect on the inflammation markers represented by the elevation in tumor necrosis factor (TNFα) and DNA damage. Administration of curcumin or curcumin NPs in TAA-intoxicated rats significantly (p < .001, p < .0001) alleviates liver injury by correcting antioxidant status, inflammatory markers, and oxidative stress. The results of comparing TAA-intoxicated rats treated with curcumin NPs to TAA-intoxicated rats treated with bulk curcumin revealed that the ameliorative effect of nanocurcumin was stronger. These observations concluded that nanoparticle formulation can increase curcumin bioavailability and solubility, enhancing its antioxidant and anti-inflammatory efficiency, resulting in greater potential against thioacetamide-induced hepatotoxicity in rats.


Assuntos
Curcumina , Nanopartículas , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Tioacetamida/toxicidade , Fígado , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Estresse Oxidativo , Anti-Inflamatórios/farmacologia , Nanopartículas/uso terapêutico
7.
Sensors (Basel) ; 23(16)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631753

RESUMO

Modern active distribution networks (ADNs) witness increasing complexities that require efforts in control practices, including optimal reactive power dispatch (ORPD). Deep reinforcement learning (DRL) is proposed to manage the network's reactive power by coordinating different resources, including distributed energy resources, to enhance performance. However, there is a lack of studies examining DRL elements' performance sensitivity. To this end, in this paper we examine the impact of various DRL reward representations and hyperparameters on the agent's learning performance when solving the ORPD problem for ADNs. We assess the agent's performance regarding accuracy and training time metrics, as well as critic estimate measures. Furthermore, different environmental changes are examined to study the DRL model's scalability by including other resources. Results show that compared to other representations, the complementary reward function exhibits improved performance in terms of power loss minimization and convergence time by 10-15% and 14-18%, respectively. Also, adequate agent performance is observed to be neighboring the best-suited value of each hyperparameter for the studied problem. In addition, scalability analysis depicts that increasing the number of possible action combinations in the action space by approximately nine times results in 1.7 times increase in the training time.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34501865

RESUMO

The present study was performed to fabricate a titanium dioxide (TiO2) nanocatalyst with proper characteristics for the removal of some insecticides (dimethoate and methomyl) from aqueous media. A TiO2 catalyst of regular (TiO2-commercial-/H2O2/UV) or nano (TiO2-synthesized-/H2O2/UV) size was employed as an advanced oxidation process by combining it with H2O2 under light. Moreover, the total detoxification of insecticides after treatment with the most effective system (TiO2(s)/H2O2/UV) was also investigated through exploring the biochemical alterations and histopathological changes in the liver and kidneys of the treated rats. Interestingly, the present study reported that degradation rates of the examined insecticides were faster using the TiO2 catalyst of nano size. Complete degradation of the tested insecticides (100%) was achieved under the TiO2(s)/H2O2/UV system after 320 min of irradiation. The half-life values of the tested insecticides under H2O2/TiO2(c)/UV were 43.86 and 36.28 for dimethoate and methomyl, respectively, whereas under the H2O2/TiO2(c)/UV system, the half-life values were 27.72 and 19.52 min for dimethoate and methomyl, respectively. On the other hand, no significant changes were observed in the biochemical and histopathological parameters of rats administrated with water treated with TiO2(s)/H2O2/UV compared to the control, indicating low toxicity of the TiO2 nanocatalyst-. Altogether, the advanced oxidation processes using TiO2 nanocatalyst can be considered as a promising and effective remediation technology for the complete detoxification of methomyl and dimethoate in water. However, further future research is needed to identify the possible breakdown products and to verify the safety of the used nanomaterials.


Assuntos
Inseticidas , Poluentes Químicos da Água , Animais , Catálise , Peróxido de Hidrogênio , Inseticidas/toxicidade , Oxirredução , Ratos , Titânio , Raios Ultravioleta , Água , Poluentes Químicos da Água/toxicidade
9.
J Hepatobiliary Pancreat Sci ; 28(9): e40-e41, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34053195

RESUMO

Highlight Elshair and colleagues describe a novel technique which could be applied for drainage of any paragastric fluid collection, including pseudocyst and abscess. In comparison to the oblique-view echoendoscope, the forward-viewing echoendoscope allows concurrent stent-in-stent placement over the same axis. Double-pit stent deployment inside the metal stent prevents bleeding and metallic-stent kinking.


Assuntos
Pseudocisto Pancreático , Pancreatite , Esplenopatias , Abscesso/diagnóstico por imagem , Abscesso/etiologia , Abscesso/cirurgia , Drenagem , Endossonografia , Humanos , Pseudocisto Pancreático/diagnóstico por imagem , Pseudocisto Pancreático/cirurgia , Pancreatite/diagnóstico por imagem , Pancreatite/etiologia , Pancreatite/terapia , Esplenopatias/diagnóstico por imagem , Esplenopatias/etiologia , Esplenopatias/cirurgia , Stents
10.
J Hepatobiliary Pancreat Sci ; 28(4): e11-e12, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539660

RESUMO

Highlight For migrating stent removal, Elshair and colleagues recommend using a double-channel scope and two biopsy forceps. The stent is fixed with one of the forceps and its proximal end is caught with the other while applying countertraction. The proximal end is cut, and the stent is safely removed through the duodenum.


Assuntos
Drenagem , Endossonografia , Biópsia , Humanos , Stents/efeitos adversos , Instrumentos Cirúrgicos
11.
Animals (Basel) ; 10(12)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33255611

RESUMO

Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds' levels.

12.
Biomed Res Int ; 2020: 2732958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219129

RESUMO

Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.


Assuntos
Extratos Vegetais/farmacologia , Punica granatum/química , Sementes/química , Doenças Testiculares/tratamento farmacológico , Testículo/efeitos dos fármacos , Tramadol/efeitos adversos , Analgésicos Opioides , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Espermátides/efeitos dos fármacos , Espermatozoides/metabolismo , Doenças Testiculares/patologia , Testículo/patologia
13.
J Clin Endocrinol Metab ; 101(12): 4521-4531, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27525530

RESUMO

CONTEXT: Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHR underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken. OBJECTIVE: Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS. Patients, Design, and Setting: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. PATIENTS, DESIGN, AND SETTING: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. RESULTS: Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG (12), TPO (four), DUOX2 (two), and TSHR (one). Ten cases harbored triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three), and DUOX2 and TG (six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases. CONCLUSIONS: The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (∼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated.


Assuntos
Autoantígenos/genética , Hipotireoidismo Congênito/genética , Iodeto Peroxidase/genética , Proteínas de Ligação ao Ferro/genética , Receptores da Tireotropina/genética , Tireoglobulina/genética , Humanos , Mutação , Linhagem , Fenótipo
14.
Toxicol Ind Health ; 32(1): 177-82, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24081634

RESUMO

Boldenone (BOL) is an androgenic steroid that improves the growth and food conversion in food-producing animals. In most countries worldwide, this anabolic steroid is forbidden for human uses and meat production as it was developed for veterinary use. Recently, BOL is used by bodybuilders in both off season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the physiological and biochemical changes in rabbits after injection with the growth promoter BOL. A total of 32 adult New Zealand rabbits were divided into four groups, where the control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. The remaining three experimental groups included animals that received one, two and three intramuscular injections of 5 mg/kg body weight BOL, respectively, and were dissected after 3, 6 and 9 weeks, respectively. The animals from practice appeared healthy and did not show clinical signs of disease and none of the rabbits died during the experimental period. Serum total protein, globulin, alanine aminotransferase, asparate aminotransferase, urea, creatinine, testosterone, luteinizing hormone and follicle-stimulating hormone levels were significantly increased while serum direct bilirubin, albumin and albumin/globulin ratio were significantly decreased (p < 0.05) after one, two and three intramuscular injections of BOL as compared to their relative values in the control group. These findings explain the common phenomena in athletes and bodybuilders who suffer from infertility, renal and hepatic alterations following injection with some drugs as steroids (BOL) to build muscles.


Assuntos
Anabolizantes/toxicidade , Testosterona/análogos & derivados , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Fenômenos Químicos , Creatinina/sangue , Hormônio Foliculoestimulante/sangue , Globulinas/metabolismo , Hormônio Luteinizante/sangue , Masculino , Coelhos , Albumina Sérica/metabolismo , Testosterona/sangue , Testosterona/toxicidade , Ureia/sangue
16.
Hepat Mon ; 13(12): e13721, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24403912

RESUMO

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a globally serious public health issue. OBJECTIVES: In this study, we investigated CC chemokine receptor 5 (CCR5-59029) polymorphism which is considered an important component of the immune system in determining the outcome of HCV infection. Its critical role as a marker in response to interferon therapy of HCV infection is also investigated besides its effect on other clinical patient factors. PATIENTS AND METHODS: This study was conducted on 82 Egyptian patients with chronic Hepatitis C Virus (HCV) infection who received PEG-INF + Ribavirin treatment for 48 weeks. The study was also conducted on 50 healthy controls (with negative results for HCV antibody and RNA PCR). Full history of patients in this study was recorded. Clinical and histological examinations, qualitative HCV nested RT-PCR, quantitative real -time PCR, and genotyping of HCV RNA genome were performed. CCR5-59029 polymorphism with nucleotide substitution from G to A was amplified. The amplicons were digested with restriction endonuclease Bsp 1286I, and produced RFLPs of the CCR5 genotypes were determined. RESULTS: The present study showed a significant association between the functional SNP of CCR5 gene and the viral response to interferon in chronic HCV Egyptian patients. It was shown that the higher fibrosis stages (F2-F4) had significant association with nonresponse to treatment compared to the lower fibrosis stages (F0-F1) (95% confidence: 5.497 - 55.074, P = 0.0001). In addition, worse liver activity grade (A2-A3) had a very highly significant association with non-responder HCV patients compared to those with better liver activity grade (A1) (95% confidence: 2.242 - 20.974, P = 0.0007). Most importantly HCV patients with G allele had a high significant association with nonresponse to treatment, higher fibrosis stages and worse liver activity grades, while the A allele had a high significant association with sustained response, low fibrosis stages and relatively better liver activity grade (95% confidence: 3.347 - 15.036, P = 0.0001). CONCLUSIONS: SNPs within the CCR5 gene should be considered as an important factor used in combination with other host gene SNPs when developing a mathematical model for anticipating response to HCV therapy.

17.
Diabetes Care ; 36(3): 505-12, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23150280

RESUMO

OBJECTIVE: Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because it has impact on the phenotype and recurrence risk for families. We have determined the genotype, phenotype, and epigenotype of the first 10 families to alert health professionals to this newly described genetic subgroup of diabetes. RESEARCH DESIGN AND METHODS: The 10 families (14 homozygous/compound heterozygous individuals) with ZFP57 mutations were ascertained through TNDM1 diagnostic testing. ZFP57 was sequenced in probands and their relatives, and the methylation levels at multiple maternally and paternally imprinted loci were determined. Medical and family histories were obtained, and clinical examination was performed. RESULTS: The key clinical features in probands were transient neonatal diabetes, intrauterine growth retardation, macroglossia, heart defects, and developmental delay. However, the finding of two homozygous relatives without diabetes and normal intelligence showed that the phenotype could be very variable. The epigenotype always included total loss of methylation at the TNDM1 locus and reproducible combinations of differential hypomethylation at other maternally imprinted loci, including tissue mosaicism. CONCLUSIONS: There is yet no clear genotype-epigenotype-phenotype correlation to explain the variable clinical presentation, and this results in difficulties predicting the prognosis of affected individuals. However, many cases have a more severe phenotype than seen in other causes of TNDM1. Further cases and global epigenetic testing are needed to clarify this.


Assuntos
Metilação de DNA/genética , Diabetes Mellitus Tipo 1/genética , Impressão Genômica/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Fenótipo
18.
Reprod Sci ; 19(3): 253-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22383777

RESUMO

Recently, boldenone (androgenic steroid) is used in improvement of the growth and food conversion in food-producing animals. In addition, it is used by bodybuilders during both off-season and precontest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the possible effect of growth promoter boldenone undecylenate on the structure and functions of rabbit testes. A total of 32 adult New Zealand rabbits were divided into 4 groups. The first group in the control group includes animals that were intramuscularly injected with olive oil and dissected after 3 weeks. Three experimental groups include animals that receive 1, 2, and 3 intramuscular injections of 5 mg/kg body weight boldenone, and dissected after 3, 6, and 9 weeks, respectively. Treating rabbits with boldenone increased the testosterone levels compared to the control group. Seminiferous tubules of the rabbit testis treated with boldenone showed reduced development and degeneration of the germinal epithelium, leading to debris and syncytial cell formation in the lumina of seminiferous tubules. Our immunohistochemical results indicated severe reduction in proliferating cell nuclear antigen-positive spermatogonia in boldenone-treated animals as compared to the control group. These findings explain the common phenomena among athletics and bodybuilders who suffer from infertility as they were injected with some drugs such as steroids (boldenone) to build muscles.


Assuntos
Anabolizantes/toxicidade , Androgênios/toxicidade , Testículo/efeitos dos fármacos , Testículo/patologia , Testosterona/análogos & derivados , Animais , Doping nos Esportes , Infertilidade Masculina/induzido quimicamente , Masculino , Substâncias para Melhoria do Desempenho/toxicidade , Coelhos , Testículo/metabolismo , Testosterona/toxicidade , Drogas Veterinárias/toxicidade
19.
Toxicol Ind Health ; 28(3): 262-70, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22331425

RESUMO

Thyroid hormones have marked effects on the growth, development, and metabolic function of virtually all organs and tissues. Thyroid status is an important determinant of cardiovascular function. The present work studied the histopathological and ultrastructural changes in the hypothyroid rat left ventricle at post-pubertal stage, in addition to the ameliorating role of folic acid. A total of 50 male albino rats were randomly divided into 5 groups (group I, control; group II, folic acid; group III, propylthiouracil-induced hypothyroid rats; group IV, co-treatment with folic acid; group V, post-treatment). In order to ensure the hypothyroid state, the level of serum triiodothyronine (T(3)) and thyroid stimulating hormone (TSH) through the dose period was regularly determined. The TSH levels were significantly higher while T(3) levels were significantly lower in hypothyroid rats when compared to control group. The high-performance liquid chromatography analysis showed an increase in homocysteine (Hcy) in the hypothyroid rats group when compared to the control group. The histopathological studies of the ventricle in hypothyroid rats revealed hydrophobic changes in myofibrillar structure with striations, myocardial atrophy, nuclear pyknosis, cytoplasmic vacuoles, and cytoplasmic eosinophilia. Transmission electron micrographs in the myocardium of hypothyroid rats revealed a marked reduction in muscle fibre mass, a marked degeneration of muscle fibres, swollen mitochondria, dilated sarcoplasmic reticulum and more prominent perinuclear oedema observed in the cardiac myocytes. In co-treated hypothyroid rats with folic acid, a regular arrangement of muscle fibres, mild swelling of myofibrillar structure with striations and no continuity with adjacent myofibrils were observed while the post-treated hypothyroid rat with folic acid showed normal architecture of myofibrillar structure with striations and continuity with adjacent myofibrils. In conclusion, our results indicated that folic acid had ameliorative effect against cardiac damage induced by 6-n-propyl-2-thiouracil and the best results were found in case of using the folic acid as an adjuvant therapy after returning to the euthyroid state.


Assuntos
Ácido Fólico/farmacologia , Hipotireoidismo/patologia , Miocárdio/patologia , Propiltiouracila/toxicidade , Substâncias Protetoras/farmacologia , Animais , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Ventrículos do Coração/ultraestrutura , Histocitoquímica , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/ultraestrutura , Ratos
20.
J Egypt Soc Parasitol ; 40(1): 245-58, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20503602

RESUMO

This study investigated the effect of myrrh extract on different developmental stages of Schistosoma mansoni. Sixty albino mice were used and divided into three main groups: GI (control group), GII (infected group) and GIII (infected-treated group). The last group was further divided into 3 subgroups where the drug was administered in a dose of 500 mg/kg body weight for 5 days starting on the 1st day PI for IIIA, on the 21st day PI for IIIB and on the 45th day PI for IIIC. A morphometric study was performed for the mean number and perimeter of granulomas. In GII, typical bilharzial granulomas were frequently encountered in the portal tracts with numerous eosinophils, collagen fiber deposition and reticular fiber condensation. Hepatocytes revealed vacuolation, nuclear affection and depletion of glycogen. In GIII, granulomas were less frequently observed with apparent decrease of eosinophils. The maximum effect of the drug was observed in SGs IIIB and IIIC as detected by significant decrease in the mean number and size of granulomas, paucity of eosinophils, decreased fibrosis and reticular fibers and the restoration of the glycogen content in the hepatocytes. The present data proved that myrrh has a valuable schistosomicidal effect against different stages of S. mansoni. This chemotherapeutic effect was more evident when the drug was given to infected mice on the 21st as well as on the 45th day PI.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológico , Terpenos/química , Terpenos/farmacologia , Animais , Humanos , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos
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