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1.
Mol Divers ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722455

ABSTRACT

Visceral Leishmaniasis (VL), the second neglected tropical disease caused by various Leishmania species, presents a significant public health challenge due to limited treatment options and the absence of vaccines. The agent responsible for visceral leishmaniasis, also referred to as "black fever" in India, is Leishmania donovani. This study focuses on L. donovani Minichromosome maintenance 10 (LdMcm10), a crucial protein in the DNA replication machinery, as a potential therapeutic target in Leishmania therapy using in silico and in vitro approaches. We employed bioinformatics tools, molecular docking, and molecular dynamics simulations to predict potential inhibitors against the target protein. The research revealed that the target protein lacks homologues in the host, emphasizing its potential as a drug target. Ligands from the DrugBank database were screened against LdMcm10 using PyRx software. The top three compounds, namely suramin, vapreotide, and pasireotide, exhibiting the best docking scores, underwent further investigation through molecular dynamic simulation and in vitro analysis. The observed structural dynamics suggested that LdMcm10-ligand complexes maintained consistent binding throughout the 300 ns simulation period, with minimal variations in their backbone. These findings suggest that these three compounds hold promise as potential lead compounds for developing new drugs against leishmaniasis. In vitro experiments also demonstrated a dose-dependent reduction in L. donovani viability for suramin, vapreotide, and pasireotide, with computed IC50 values providing quantitative metrics of their anti-leishmanial efficacy. The research offers a comprehensive understanding of LdMcm10 as a drug target and provides a foundation for further investigations and clinical exploration, ultimately advancing drug discovery strategies for leishmaniasis treatment.

2.
BMJ Open ; 14(5): e080623, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702079

ABSTRACT

OBJECTIVE: This study aimed to investigate the burden of the COVID-19 pandemic on tuberculosis (TB) trends, patient demographics, disease types and hospitalisation duration within the Respiratory Medicine Department over three distinct phases: pre-COVID-19, COVID-19 and post-COVID-19. DESIGN: Retrospective analysis using electronic medical records of patients with TB admitted between June 2018 and June 2023 was done to explore the impact of COVID-19 on patients with TB. The study employed a meticulous segmentation into pre-COVID-19, COVID-19 and post-COVID-19 eras. SETTING: National Institute of Medical Science Hospital in Jaipur, Rajasthan, India. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome includes patients admitted to the Respiratory Medicine Department of the hospital and secondary outcome involves the duration of hospital stay. RESULTS: The study encompassed 1845 subjects across the three eras, revealing a reduction in TB incidence during the post-COVID-19 era compared with the pre-COVID-19 period (p<0.01). Substantial demographic shifts were observed, with 5.2% decline in TB incidence among males in the post-COVID-19 era (n=529) compared with the pre-COVID-19 era (n=606). Despite the decrease, overall TB incidence remained significantly higher in males (n=1460) than females (n=385), with consistently elevated rates in rural (65.8%) as compared with the urban areas (34.2%). Extended hospital stays were noted in the post-COVID-19 era compared with the pre-COVID-19 era (p<0.01). CONCLUSION: The study underscores the influence of the COVID-19 pandemic on the TB landscape and hospitalisation dynamics. Notably, patient burden of TB declined during the COVID-19 era, with a decline in the post-COVID-19 era compared with the pre-COVID-19 era. Prolonged hospitalisation in the post-COVID-19 period indicates the need for adaptive healthcare strategies and the formulation of public health policies in a post-pandemic context. These findings contribute to a comprehensive understanding of the evolving TB scenario, emphasising the necessity for tailored healthcare approaches in the aftermath of a global health crisis.


Subject(s)
COVID-19 , Hospitalization , SARS-CoV-2 , Tertiary Care Centers , Tuberculosis , Humans , COVID-19/epidemiology , Male , India/epidemiology , Retrospective Studies , Female , Hospitalization/statistics & numerical data , Tertiary Care Centers/statistics & numerical data , Adult , Middle Aged , Tuberculosis/epidemiology , Length of Stay/statistics & numerical data , Incidence , Aged , Young Adult , Pandemics , Adolescent
3.
Indian J Crit Care Med ; 28(2): 181-182, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38323247

ABSTRACT

How to cite this article: Magoon R, Sharma AG, Yadav N, Choupoo NS. Hemodynamics: Strangers to Lung-kidney Crosstalk in ARDS? Indian J Crit Care Med 2024;28(2):177-178.

4.
J Phys Chem B ; 127(51): 11011-11022, 2023 Dec 28.
Article in English | MEDLINE | ID: mdl-37972382

ABSTRACT

The water microstructure around propofol plays a crucial role in controlling their solubility in the binary mixture. The unusual nature of such a water microstructure can influence both translational and reorientational dynamics, as well as the water hydrogen bond network near propofol. We have carried out all-atom molecular dynamics simulations of five different compositions of the propylene glycol (PG)/water binary mixture containing propofol (PFL) molecules to investigate the differential behavior of water microsolvation shells around propofol, which is likely to control the propofol solubility. It is evident from the simulation snapshots for various compositions that the PG at high molecular ratio favors the water cluster and extended chainlike network that percolates within the PG matrix, where the propofol is in the dispersed state. We estimated that the radial distribution function indicates higher ordered water microstructure around propofol for high PG content, as compared to the lower PG content in the PG/water mixture. So, the hydrophilic PG regulates the stability of the water micronetwork around propofol and its solubility in the binary mixture. We observed that the translational and rotational mobility of water belonging to the propofol microsolvation shell is hindered for high PG content and relaxed toward the low PG molecular ratio in the PG/water mixture. It has been noticed that the structural relaxation of the hydrogen bond formed between the propofol and the water molecules present in the propofol microsolvation shell for all five compositions is found to be slower for high PG content and becomes faster on the way to low PG content in the mixture. Simultaneously, we calculated the intermittent residence time correlation function of the water molecules belonging to the microsolvation shell around the propofol for five different compositions and found a faster short time decay followed up with long time components. Again, the origin of such long time decay is primarily from the structural relaxation of the microsolvation shell around the propofol, where the high PG content shows the slower structural relaxation that turns faster as the PG content approaches to the other end of the compositions. So, our studies showed that the slower structural relaxation of the microsolvation shell around propofol for a high PG molecular ratio in the PG/water mixture correlate well with the extensive ordering of the water microstructure and restricted water mobility and facilitates the dissolution process of propofol in the binary mixture.

5.
Crit Rev Food Sci Nutr ; : 1-18, 2023 Jun 19.
Article in English | MEDLINE | ID: mdl-37335120

ABSTRACT

One of the emerging non-digestible oligosaccharide prebiotics is ß-mannooligosaccharides (ß-MOS). ß-MOS are ß-mannan derived oligosaccharides, they are selectively fermented by gut microbiota, promoting the growth of beneficial microorganisms (probiotics), whereas the growth of enteric pathogens remains unaffected or gets inhibited in their presence, along with production of metabolites such as short-chain fatty acids. ß-MOS also exhibit several other bioactive properties and health-promoting effects. Production of ß-MOS using the enzymes such as ß-mannanases is the most effective and eco-friendly approach. For the application of ß-MOS on a large scale, their production needs to be standardized using low-cost substrates, efficient enzymes and optimization of the production conditions. Moreover, for their application, detailed in-vivo and clinical studies are required. For this, a thorough information of various studies in this regard is needed. The current review provides a comprehensive account of the enzymatic production of ß-MOS along with an evaluation of their prebiotic and other bioactive properties. Their characterization, structural-functional relationship and in-vivo studies have also been summarized. Research gaps and future prospects have also been discussed, which will help in conducting further research for the commercialization of ß-MOS as prebiotics, functional food ingredients and therapeutic agents.

6.
J Ultrasound Med ; 42(8): 1819-1827, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36851848

ABSTRACT

OBJECTIVES: 1) To compare ultrasound (US) examination and fiberoptic laryngoscopy (FOL) for confirmation of laryngeal mask airway (LMA) placement. 2) To evaluate the necessity for reinsertion of LMA based on FOL. METHODS: This prospective observational study included 100 adult patients of American Society of Anesthesiologists (ASA) Grade I and II, undergoing elective surgery under General Anesthesia requiring Proseal LMA™ placement as an airway device. LMA placement was first confirmed by clinical tests. Clinically acceptable patients were further assessed by US and categorized as acceptable (US-A) or unacceptable (US-U) and again by FOL as (FOL-A and FOL-U). Categorical variables presented in number, percentage (%), and continuous variables presented as mean ± SD and median. Inter-rater kappa agreement was used to find out the strength of agreement of acceptability between FOL and US. RESULTS: The LMA placement was clinically acceptable in 82% of patients on first attempt. FOL had 63% (FOL-A) acceptable LMA placement as compared with US examination which had 56% (US-A). In 85% of patients, US and FOL findings were in good agreement with each other for LMA placement (κ = 0.690 and P < .05). In all patients of FOL of unacceptable (FOL-U) category (37%), LMA was replaced with endotracheal tube. CONCLUSION: US provides a safe, non-invasive, and real-time dynamic assessment with 85% diagnostic accuracy for confirmation of LMA placement as compared with FOL.


Subject(s)
Laryngeal Masks , Adult , Humans , Laryngoscopy , Intubation, Intratracheal , Anesthesia, General , Ultrasonography
7.
J Turk Ger Gynecol Assoc ; 23(3): 199-210, 2022 Sep 05.
Article in English | MEDLINE | ID: mdl-36065987

ABSTRACT

Mercury is a toxic heavy metal. Humans are exposed to mercury through several sources including environmental, occupational, contaminated food and water and from mercury-containing dental amalgam. Mercury exposure is known to harm the nervous system profoundly, and have a negative impact on digestive and immune systems, and other organs. To review and discuss the effect of mercury exposure through environmental or occupational routes on human reproduction, pregnancy, and its outcome. Published information about the potential toxic effects of mercury on human reproduction were collected and summarized. Literature was identified by systematic search using relevant keywords. Literature review revealed a number of negative impacts of mercury on human reproduction. These included effects on semen quality, including reduced sperm count, motility, and changes in morphology that may reduce fertility potential. There may also be an effect in changing reproductive hormone levels. Mercury exposure might also affect pregnancy but the data concerning mercury effects on female reproduction are limited except for some data about mercury exposure and poor pregnancy outcomes. Available data indicate that mercury exposure may have a toxicity effect on reproductive potential, especially in males. Prenatal mercury exposure may affect pregnancy or its outcome and this appears to be dependent upon dose, duration, and timing of exposure. Nutritional status of exposed individual might also influence the impact of mercury.

9.
J Family Med Prim Care ; 11(10): 6274-6279, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36618159

ABSTRACT

Background: Worldwide, one million cases of bacterial meningitis are estimated to occur and 200,000 of them die annually. Case fatality rates vary with age at the time of illness and the species of bacterium causing infection. In view of variable clinical features and complication rates in various studies, the present study was planned to assess the clinical and laboratory profile of patients with acute bacterial meningitis and analyze the therapeutic response and short-term sequelae. Materials: This study was conducted in the department of pediatrics at Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak. A total of 50 pediatric patients with signs and symptoms of acute bacterial meningitis who satisfied the inclusion or selection criteria were enrolled in the study. Appropriate statistical tests were applied for analysis and trial registry was done with PGIMS. Results: In the present study, slightly more males (54%) were found than females (46%). The sequelae and mortality were 33.3%, 26.1% and 7.4%, 8.7% in males and females, respectively. There were higher chances of sequelae or mortality in males as compared to females (OR 1.289, 95% CI 0.073-6.11, P > 0.05). Predominant cells were polymorphonuclear (PMN) cells except in >120 months age group where both PMN (50%) and mononuclear (50%) cells were equally visualized. Mean CSF protein was slightly higher in 2-24 months age group. Conclusion: We compared the group with sequelae with the group with no sequelae and found neurological deficit (P < 0.01), and presence of complications (P < 0.01) were significantly associated with sequelae.

10.
ISME J ; 15(10): 3019-3033, 2021 10.
Article in English | MEDLINE | ID: mdl-33953363

ABSTRACT

Antibiotic resistance in microbial communities reflects a combination of processes operating at different scales. In this work, we investigate the spatiotemporal dynamics of bacterial colonies comprised of drug-resistant and drug-sensitive cells undergoing range expansion under antibiotic stress. Using the opportunistic pathogen Enterococcus faecalis with plasmid-encoded ß-lactamase, we track colony expansion dynamics and visualize spatial patterns in fluorescently labeled populations exposed to antibiotics. We find that the radial expansion rate of mixed communities is approximately constant over a wide range of drug concentrations and initial population compositions. Imaging of the final populations shows that resistance to ampicillin is cooperative, with sensitive cells surviving in the presence of resistant cells at otherwise lethal concentrations. The populations exhibit a diverse range of spatial segregation patterns that depend on drug concentration and initial conditions. Mathematical models indicate that the observed dynamics are consistent with global cooperation, despite the fact that ß-lactamase remains cell-associated. Experiments confirm that resistant colonies provide a protective effect to sensitive cells on length scales multiple times the size of a single colony, and populations seeded with (on average) no more than a single resistant cell can produce mixed communities in the presence of the drug. While biophysical models of drug degradation suggest that individual resistant cells offer only short-range protection to neighboring cells, we show that long-range protection may arise from synergistic effects of multiple resistant cells, providing surprisingly large protection zones even at small population fractions.


Subject(s)
Ampicillin , Anti-Bacterial Agents , Ampicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial , Enterococcus faecalis , Microbial Sensitivity Tests , beta-Lactamases/genetics
11.
Rev Environ Health ; 36(4): 565-575, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-33544535

ABSTRACT

Excessive air pollution, both ambient and indoor are might be detrimental to human wellbeing and are related to morbidity and mortality, it may also affect the reproductive function and its outcome. It is a recognized fact that air pollution contains several toxicants, gases, particulate matter, toxic metals etc. Some of them might affect reproductive and developmental process and a few are persistent. The information accessible on air pollution to human male reproduction is stated to affect semen quality by diminishing one or more sperm quality parameters i.e., sperm morphology, concentration, motility etc. and may causes sperm DNA damage, these might alter the fertility potential which in turn affect pregnancy or its outcome. The impact might be related to the pollutant's concentration and duration of exposure. The data on impact of air contamination on endocrine function are inadequate, inconsistence and the diversity of existence of air contaminants in area to area and multiplicity in semen quality parameters assessed in various studies as well as study design variables complicated the problem of evaluation of impact of air pollution on male reproduction. The data available suggests the air pollution is might be injurious to human male reproductive health, which depends upon amounts of air pollutants in the air, duration of exposure etc. but more comprehensive data are needed to substantiate the findings. The data are also needed on indoor air pollution on reproduction as people are might be subjected to greater quantities of some of the indoor air pollutants as compared to ambient air pollution.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , Humans , Male , Particulate Matter/analysis , Particulate Matter/toxicity , Reproductive Health , Semen Analysis
12.
Environ Sci Pollut Res Int ; 28(16): 20517-20536, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33410021

ABSTRACT

One of the most common toxicant prevailing in our environment is the arsenic. The present study is an attempt to investigate the effects of some of the common flavonoids, such as biochanin A (BCA), phloretin, and epigallocatechin-3-gallate (EGCG), on arsenic toxicity in the Swiss albino mice. For this purpose, mice were orally treated with sodium meta-arsenite (20 mg/kg bw/day), along with co-administration of BCA (50 mg/kg bw/day), phloretin (50 mg/kg bw/day), and EGCG (40 mg/kg bw/day) for the 2-week duration. All the mice were euthanized at the end of the treatment period, and the observations were made in the following parameters. Arsenic reduced the sperm motility as compared with the control (p < 0.05) and was restored back to the normal status with the flavonoids treatment significantly (p < 0.05). The arsenic concentrations in the kidney and liver tissues were found significantly reduced with all the flavonoids co-treatment (p < 0.001). There was a reduction in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione S-transferase (GST) antioxidant markers, with the increased lipid peroxidation (LPO), protein carbonyl content (PCC), and catalase (CAT) levels in the arsenic-intoxicated mice performed in the different tissues. The biochemical homeostasis alterations were well correlated with the estimations of cholinesterase enzyme levels in the brain tissues (p < 0.05) along with DNA damage analysis (Comet) carried out in the blood cells (p < 0.05). These above results are well corroborated with the histopathological findings performed in the brain tissue, along with the increased upregulation seen in the Nrf2 signalling, with all the flavonoid co-treatment carried in the kidney tissue. The administration of BCA, phloretin, and EGCG, in a major way, reversed the alterations in the abovementioned parameters in the arsenic-intoxicated mice. Our findings revealed the beneficial effects of the flavonoids against the arsenic-induced toxicity, due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2 signaling pathway.


Subject(s)
Arsenic , Animals , Antioxidants/metabolism , Arsenic/metabolism , Arsenic/toxicity , Catechin/analogs & derivatives , Genistein , Humans , Lipid Peroxidation , Liver/metabolism , Male , Mice , Oxidative Stress , Phloretin/pharmacology , Protein Carbonylation , Sperm Motility
13.
J Biomol Struct Dyn ; 39(18): 6853-6869, 2021 11.
Article in English | MEDLINE | ID: mdl-32752940

ABSTRACT

To overcome the obstacle of anti-cancer therapy significant attention has been drawn for improving drug delivery system. Since recent past, different approaches were applied using synthetic or natural derivatives for improving efficacy of anti-cancer drugs in cancer therapeutics. Gallic acid (GA) is a natural polyphenol, which exhibits a broad spectrum of biological activities, but its therapeutic application was limited due to poor bioavailability and toxicity. In the present study, we had conjugated the GA with PAMAM dendrimers and proposed the insights of molecular mechanism on inhibition of cell proliferation and programmed cell death through apoptotic pathway in human colon carcinoma cells. GA was chemically conjugated with 4.0 G PAMAM dendrimer at outer surface and characterized by different biophysical methods. We further examined its bioavailability, anti-cancer activity and explored the molecular mechanism of programmed cell death signaling in HCT116 cells. The results show that PAMAM-GA conjugate inhibits cell proliferation of different origin of cancer cells, improves cellular uptake of GA, inhibits colonogenic ability, restricts cancer cell migration by down regulating the expression of MMP-9, inhibits NF-kB activation and release of pro-inflammatory cytokines to manifest apoptotic cell death in HCT 116 cells rather than necrosis. On other hand, PAMAM-GA conjugate showed negligible cytotoxic response as compared to the free Gallic acid to the normal cells. In conclusion, findings of this study revealed that PAMAM-GA conjugate improves the bioavailability of GA and specificity towards cancer cellsto manifests apoptotic cell death. This indispensable approach may be beneficial for the revolution of anti-cancer therapy.Communicated by Ramaswamy H. Sarma.


Subject(s)
Carcinoma , Colonic Neoplasms , Dendrimers , Apoptosis , Cell Movement , Cell Proliferation , Colonic Neoplasms/drug therapy , Gallic Acid/pharmacology , Humans
14.
Rev Environ Health ; 34(4): 403-414, 2019 Dec 18.
Article in English | MEDLINE | ID: mdl-31603861

ABSTRACT

Arsenic (As) toxicity has become a public health and environmental problem, which is a serious issue in certain parts of the world. Many people are exposed to As through contaminated drinking water, food and soil, through occupation, etc. Chronic As exposure is linked to various hostile health effects including skin problems, cancer, diabetes, cardiovascular disease, reproductive and developmental and neurological problems in exposed subjects. Experimental existing data indicate that chronic As exposure affects the nervous system by impairing the nerve and brain tissues of the exposed animals, and clinical studies indicate that As exposure leads to both central nervous system and peripheral nervous system impairments and also causes depression, memory impairment and difficulty in problem solving, affects body coordination, etc. Various prenatal and postnatal studies with respect to As exposure also suggest that developing offspring and young children are susceptible to As exposure. The only solution to this serious health problem is to stop occupational As exposure and provide As free drinking water to the affected population.


Subject(s)
Arsenic/toxicity , Environmental Exposure/adverse effects , Nervous System Diseases/chemically induced , Water Pollutants, Chemical/toxicity , Animals , Humans , Nervous System Diseases/pathology , Nervous System Diseases/physiopathology
15.
PLoS Comput Biol ; 15(5): e1006977, 2019 05.
Article in English | MEDLINE | ID: mdl-31120877

ABSTRACT

The effectiveness of a mass vaccination program can engender its own undoing if individuals choose to not get vaccinated believing that they are already protected by herd immunity. This would appear to be the optimal decision for an individual, based on a strategic appraisal of her costs and benefits, even though she would be vulnerable during subsequent outbreaks if the majority of the population argues in this manner. We investigate how voluntary vaccination can nevertheless emerge in a social network of rational agents, who make informed decisions whether to be vaccinated, integrated with a model of epidemic dynamics. The information available to each agent includes the prevalence of the disease in their local network neighborhood and/or globally in the population, as well as the fraction of their neighbors that are protected against the disease. Crucially, the payoffs governing the decision of agents vary with disease prevalence, resulting in the vaccine uptake behavior changing in response to contagion spreading. The collective behavior of the agents responding to local prevalence can lead to a significant reduction in the final epidemic size, particularly for less contagious diseases having low basic reproduction number [Formula: see text]. Near the epidemic threshold ([Formula: see text]) the use of local prevalence information can result in divergent responses in the final vaccine coverage. Our results suggest that heterogeneity in the risk perception resulting from the spatio-temporal evolution of an epidemic differentially affects agents' payoffs, which is a critical determinant of the success of voluntary vaccination schemes.


Subject(s)
Epidemics/prevention & control , Mass Vaccination/trends , Vaccination/psychology , Communicable Disease Control/trends , Communicable Diseases , Computer Simulation , Decision Making , Disease Outbreaks/prevention & control , Humans , Immunity, Herd/immunology , Models, Biological , Prevalence , Risk , Social Networking , Vaccination/trends , Vaccines
16.
Rev Environ Health ; 34(4): 327-338, 2019 Dec 18.
Article in English | MEDLINE | ID: mdl-31129655

ABSTRACT

Background Cadmium (Cd) is a non-essential toxic heavy metal, an environmental toxicant, and toxic at a low concentration, and it has no known beneficial role in the human body. Its exposure induces various health impairments including hostile reproductive health. Objective The present review discusses the information on exposure to Cd and human reproductive health impairments including pregnancy or its outcome with respect to environmental and occupational exposure. Methods The present review provides current information on the reproductive toxic potential of Cd in humans. The data were collected using various websites and consulting books, reports, etc. We have included recent data which were published from 2000 onward in this review. Results Cd exposure affects human male reproductive organs/system and deteriorates spermatogenesis, semen quality especially sperm motility and hormonal synthesis/release. Based on experimental and human studies, it also impairs female reproduction and reproductive hormonal balance and affects menstrual cycles. Based on the literature, it might be concluded that exposure to Cd at low doses has adverse effects on both human male and female reproduction and affects pregnancy or its outcome. Further, maternal prenatal Cd exposure might have a differential effect on male and female offspring especially affecting more female offspring. Hence, efforts must be made to prevent exposure to Cd. Conclusion Cd affects both male and female reproduction, impairs hormone synthesis/regulation and deteriorates pregnancy rate or its outcome even at lower doses.


Subject(s)
Cadmium/toxicity , Environmental Pollutants/toxicity , Fertility/drug effects , Reproduction/drug effects , Female , Humans , Male
17.
J Turk Ger Gynecol Assoc ; 20(4): 255-263, 2019 11 28.
Article in English | MEDLINE | ID: mdl-30821135

ABSTRACT

Polycystic ovary syndrome (PCOS) is a multifaceted disease of women with infertility that has diverse etiologic factors. Some women may have only a few PCOS-linked symptoms or mild symptoms, whereas others will have severe or all PCOS-linked symptoms. Therefore, PCOS symptoms can differ among women. PCOS is a state of hormonal imbalance, excess terminal hair (hirsutism), hair loss (alopecia), menstruation impairments, metabolic disorders, and cystic appearance on the ovaries. The cysts hamper ovulation, thus reducing the ability of women to become pregnant and result in infertility. The available data suggest that PCOS might originate in utero and the phenotypic appearance of PCOS symptoms may be developed in later life, which could be linked with host factors (endogenous) and exogenous factors like lifestyle, and dietary, environmental or occupational factors. Based upon the available information, it can be postulated that prenatal exposure to excessive androgens might be responsible for androgenization of the fetus, which in turn may alter the program of differentiating target tissues and the phenotypic characteristics of PCOS can be persuaded by exposure of female offspring to various endogenous and exogenous factors at later life. Genetic/host and environmental/lifestyle factors might be related to the pathophysiology of PCOS after prenatal exposure to androgen. Additional studies are necessary to understand the exact mechanism responsible for the manifestation of PCOS because it is a very important issue in female reproduction.

18.
Indian J Med Res ; 150(6): 532-545, 2019 12.
Article in English | MEDLINE | ID: mdl-32048617

ABSTRACT

All individuals are exposed to certain chemical, physical, biological, environmental as well as occupational factors. The data pertaining to role of these factors on female reproduction are scanty as compared to male. The available data suggest the adverse effects of certain toxicants, viz., metals such as lead, cadmium and mercury, pesticides such as bis(4-chlorophenyl)-1,1,1-trichloroethane and organic solvent such as benzene, toluene and ionizing radiation on the female reproductive system affecting directly the organ system or impacting in directly through hormonal impairments, molecular alterations, oxidative stress and DNA methylation impairing fertility as well as pregnancy and its outcomes. Thus, there is a need for awareness and prevention programme about the adverse effects of these factors and deterioration of female reproductive health, pregnancy outcome and offspring development as some of these chemicals might affect the developing foetus at very low doses by endocrine disruptive mechanism.


Subject(s)
Infertility, Male/epidemiology , Occupational Exposure/adverse effects , Oxidative Stress/drug effects , Reproduction/genetics , Benzene/toxicity , DNA Methylation/drug effects , Environmental Exposure/adverse effects , Female , Humans , Infertility, Male/chemically induced , Infertility, Male/genetics , Male , Metals/toxicity , Pesticides/toxicity , Pregnancy , Reproduction/drug effects , Reproduction/physiology
19.
Biofactors ; 44(5): 418-430, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30303271

ABSTRACT

Chlorophyllin is a water-soluble mixture of sodium-copper salts of chlorophyll with antioxidant and antimutagen properties. In this study, an attempt has been made to evaluate the effect of chlorophyllin on hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin (STZ)-administered mice. In STZ-induced diabetes, two causative factors for pancreatic ß-cell deaths are DNA alkylation and profound reactive oxygen species (ROS) generation. In this study, chlorophyllin treatment was found to be able to modulate oxidative stress and apoptosis in liver of diabetic mice. Diabetic mice exhibited a significant reduction of ROS, malondialdehyde (MDA), and protein carbonyl levels upon treatment with the chlorophyllin. However, antioxidant enzymes, such as copper-zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and catalase (CAT) showed enhanced activity as well as expression in chlorophyllin-administered diabetic mice. The hepatoprotective effect of chlorophyllin was confirmed from the decreased activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The histological and ultrastructural studies revealed the ability of chlorophyllin to restore morphological and cellular alterations as observed in STZ-induced diabetic mice. The effect of chlorophyllin on apoptosis showed the downregulation of cysteine-dependent aspartate-specific protease (caspase) 3 and caspase 9, whereas upregulation of B-cell lymphoma-2 (Bcl-2) protein, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a few apoptotic cells. In conclusion, it can be stated that chlorophyllin treatment can exert hepatoprotective effect via modulating hyperglycemia-induced oxidative stress and apoptosis in STZ-administered diabetic mice. © 2018 BioFactors, 44(5):418-430, 2018.


Subject(s)
Chlorophyllides/administration & dosage , Diabetes Mellitus, Experimental/diet therapy , Hyperglycemia/diet therapy , Liver/drug effects , Animals , Antioxidants/administration & dosage , Apoptosis/drug effects , Catalase/genetics , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Dietary Supplements , Humans , Hyperglycemia/genetics , Hyperglycemia/pathology , Liver/pathology , Mice , Mice, Inbred NOD , Oxidative Stress/drug effects , Superoxide Dismutase/genetics , Superoxide Dismutase-1/genetics
20.
Environ Sci Pollut Res Int ; 25(24): 23946-23953, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29948670

ABSTRACT

Arsenic toxicity becomes one of the major public health issues in several countries. Chronic and acute exposure to arsenic has been reported to be toxic to various systems of the human body and also observed in controlled experimental studies. The study was conducted to evaluate the neurotoxic effect of arsenic in Swiss albino mice and its amelioration by Vitamin E, Coenzyme Q10 and their combination. Swiss albino mice were treated with arsenic of 136 ppm for 15 days. The daily dose is 1/3 of LD 50 (acute) reported dose of arsenic. Thereafter, the animals were maintained either on drinking water or treated with Vitamin E (50 mg/kg bwt), Coenzyme Q10 (10 mg/kg bwt), and their combination by i.p.daily for 15 days. After the treatment, animals were sacrificed. The weight of the brain was marginally lower (ns), in arsenic-treated group as compared to control and antioxidant-protected groups. The LPO (lipid peroxidation) level was higher in arsenic-treated group, and this elevation was checked to some extent by the selected antioxidants which were statistically significant in combination of antioxidant-protected group. A significant reduction was found in GSH (reduced glutathione) level in the brain of arsenic-treated mice whereas GSH level was considerably higher in antioxidant-protected groups. Further, total thiol and total protein level were lower in arsenic-treated group. However, total thiol was significantly higher in antioxidant-protected groups. CAT (catalase) activity was significantly lower while SOD (superoxide dismutase) activity was marginally lowered in arsenic-treated group, and it was slightly higher in antioxidant-protected groups. Further, reduction in AChE (acetylcholinesterase) and BChE (butyrylcholinesterase) and motor coordination activity were also observed in arsenic-treated groups. Whereas, a higher AChE, BChE, and motor coordination activity was observed in antioxidant-protected group. These data indicate a positive role of selected antioxidant against the toxicity of arsenic in the brain of mice.


Subject(s)
Antioxidants/pharmacology , Arsenic/toxicity , Brain/drug effects , Ubiquinone/analogs & derivatives , Vitamin E/pharmacology , Acetylcholinesterase/metabolism , Animals , Antioxidants/metabolism , Brain/metabolism , Butyrylcholinesterase/metabolism , Catalase/metabolism , Glutathione/metabolism , Lipid Peroxidation/drug effects , Male , Mice , Oxidative Stress/drug effects , Superoxide Dismutase/metabolism , Ubiquinone/pharmacology
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