Band 32, Heft 5

Objectives The objective of this study is to explore the efficacy and safety of N -acetyl-cysteine (NAC) as adjuvant therapy in female infertility. Content We performed a systematic literature search of PubMed, Cochrane Library, Embase, and Ovid databases through April 2019 for Randomized Controlled Trials (RCTs) evaluating the effectiveness and safety of NAC as adjuvant therapy in female infertility. The outcomes assessed were rates of ovulation, pregnancy, miscarriage and multiple pregnancy, presented as pooled odds ratio with 95% confidence interval (CI) using the random-effects model. Heterogeneity and inconsistency of the measurements were identified through Cochrane’s Q statistic and I2 statistic. We also performed a sensitivity analysis, publication bias (using funnel plot and Begg’s test), and subgroup analysis. Summary Fifteen RCTs recruiting 2330 female receiving NAC were included. The pooled estimate showed the statistically insignificant improvement in outcomes; clinical pregnancy rate 1.55 (95% CI 0.98–2.47; I2=68%; p<0.01), ovulation rate 1.77 (95% CI 0.76–4.14; I2=90%; p<0.01), multiple pregnancy rate 0.83 (95% CI 0.34–1.99; I2=10%; p=0.31) and miscarriage rate 0.76 (95% CI= 0.37, 1.53; I2=0%; p=0.69) . NAC was found less efficacious and safe than metformin in all outcomes. Overall, NAC showed statistically insignificant (OR=0.98–2.47). Outlook NAC can be an effective adjuvant in PCOS related and unexplained female infertility. The effect could be more profound in women with high BMI, insulin resistance, and oxidative stress. However, the findings need further confirmation in well-designed randomized controlled trials to examine clinical outcomes such as live birth rate in more extended follow-up periods.

Climate change is an incessant global phenomenon and has turned contentious in the present century. Malaysia, a developing Asian country, has also undergone significant vicissitudes in climate, which has been projected with significant deviations in forthcoming decades. As per the available studies, climate changes may impact on the fertility, either via direct effects on the gonadal functions and neuroendocrine regulations or via several indirect effects on health, socioeconomic status, demeaning the quality of food and water. Malaysia is already observing a declining trend in the Total fertility rate (TFR) over the past few decades and is currently recorded below the replacement level of 2.1 which is insufficient to replace the present population. Moreover, climate changes reportedly play a role in the emergence and cessation of various infectious diseases. Besides its immediate effects, the long-term effects on health and fertility await to be unveiled. Despite the huge magnitude of the repercussion of climate changes in Malaysia, research that can explain the exact cause of the present reduction in fertility parameters in Malaysia or any measures to preserve the national population is surprisingly very scarce. Thus, the present review aims to elucidate the possible missing links by which climate changes are impairing fertility status in Malaysia.

Objectives This study aimed to access the protective effects of d -ribose- l -cysteine (DRLC) on cyclophosphamide (CPA) induced gonadal toxicity in male rats. Methods Forty-eight male Sprague-Dawley rats were divided into six groups of eight rats each. Group I the control, received distilled water (10 ml/kg), Group II received a single dose of CPA 100 mg/kg body weight intraperitoneally (i.p), Groups III and IV received a single dose of CPA at 100 mg/kg (i.p) and then were treated with DRLC at 200 mg/kg bodyweight (b.w) and 400 mg/kg b.w for 10 days, respectively. Rats in Groups V and VI received DRLC at 200 and 400 mg/kg b.w for 10 days, respectively. DRLC was administered orally. Results Results showed that CPA increased percentage of abnormal sperm cells and reduced body weight, sperm count, sperm motility, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels (p<0.05). CPA also induced oxidative stress as indicated by the increased malondialdehyde (MDA) content and reduced activities of the oxidative enzymes measured (p<0.05). Liver enzymes were elevated while the blood cells production was decreased in the rats administered CPA. DRLC supplementation enhanced the antioxidant defence system as indicated in the reduced MDA levels and increased activities of the antioxidant enzymes when compared with CPA (p<0.05). Bodyweight, sperm count, sperm motility, FSH, and testosterone levels were increased in the CPA + DRLC II group compared with CPA (p<0.05). Conclusions The results of this present study showed that DRLC has a potential protective effect on CPA-induced gonadotoxicity.

Objectives The role of the environment and climate in the transmission and case fatality rates of SARS-CoV-2 is still being investigated a year into the pandemic. Elevation and air quality are believed to be significant factors in the development of the pandemic, but the influence of additional environmental factors remains unclear. Methods We explored the relationship between the cumulative number of infections and mortality cases with climate (temperature, precipitation, solar radiation, water vapor pressure, wind), environmental data (elevation, normalized difference vegetation index or NDVI, particulate matter at 2.5 μm or PM 2.5 and NO 2 concentration), and population density in Peru. We use confirmed cases of infection from 1,287 districts and mortality in 479 districts, we used Spearman’s correlations to assess the bivariate correlation between environmental and climatic factors with cumulative infection cases, cumulative mortality and case-fatality rate. We explored district cases within the ecozones of coast, sierra, high montane forest and lowland rainforest. Results Multiple linear regression models indicate elevation, mean solar radiation, air quality, population density and green vegetation cover, as a socioeconomic proxy, are influential factors in the distribution of infection and mortality of SARS-CoV-2 in Peru. Case-fatality rate was weakly associated with elevation. Conclusions Our results also strongly suggest that exposure to poor air quality is a significant factor in the mortality of individuals below the age of 30. We conclude that environmental and climatic factors do play a significant role in the transmission and case fatality rates in Peru, however further study is required to see if these relationships are maintained over time.

Objectives Patency of ductus arteriosus (PDA) is a very common problem among extremely low birth weight infants (ELBW). Hemodynamic instability caused by PDA is associated with important morbidities. This study aims to evaluate the effects of prophylactic intravenous paracetamol on the hemodynamically significant patent ductus arteriosus (hsPDA). Methods A total of 75 infants of <28 week-gestational age were enrolled into the study which was retrospective. Prophylactic paracetamol as the experimental group and none-prophylaxis group as the control group were compared in the study. Results There were 35 subjects in the prophylactic paracetamol group (PPG), and 40 in the control group. Primary outcome measures were ductal closure, ductal diameter, grade 3–4 IVH, and repeated ibuprofen need for the treatment of hsPDA. At the time of the evaluation by echo, hsPDA, and the diameter of the ductus higher than 1 mm were found significantly lower in the PPG (p=0.004 and p=0.013). Additionally, the repeated course of ibuprofen was significantly lower in the PPG (p=0.025). Secondary outcomes were the other perinatal morbidities. According to the results of the study, the male gender is 6.6, and the paracetamol use is 5.5 times more likely to suffer from ROP. Conclusions The results of the study indicated that prophylactic paracetamol use in ELBW infants decreases the likelihood of hsPDA. The repeated course of ibuprofen for the treatment of hsPDA can be reduced. Furthermore, it can be understood that while prophylactic use of paracetamol is preventive for intraventricular hemorrhage, it does not function in the same way for retinopathy of prematurity or bronchopulmonary dysplasia. It might even worse the retinopathy of prematurity. Further prospective randomized controlled and larger sample-sized studies are needed.

Objectives Electromagnetic fields have been reported to alter electrical activities in the brain and heart. However, there is paucity of information on the potential functional alterations that magnetic fields from mobile phone could cause to the heart. This study investigated heart rate variability (HRV), blood pressure (BP) and lipid profile in Wistar rats exposed to electromagnetic field radiation from a dual transceiver mobile phone (DTrMP). Methods Twenty-one male albino Wistar rats (140–180 g) were randomly assigned to two major groups positioned 5 m apart as follows: control: no phone (n=7) and treatment group (n=14) continuously exposed to electromagnetic field from Tecno T312 DTrMP 900/1800 MHz set in silence mode. Experimental treatment consisted in 10 min calls/day, directed to this device for a period of six weeks. Seven animals from the treatment group were allowed to recover for a period of two weeks after exposure. HRV, systolic, diastolic and mean arterial BP were noninvasively investigated, while serum lipid profile and heart tissue nitric oxide (NO) activities were determined using standard procedures. Results There was significant (p<0.05) increase in systolic, diastolic, mean arterial BP and a decrease in HRV. Serum high density lipoproteins decreased, while total cholesterol, atherogenic indices, and heart NO levels increased significantly in the radiation exposed animals. The alterations observed in exposed animals remained unchanged even after the recovery period. Conclusions These results suggest that exposure to electromagnetic radiation from dual transceiver mobile phones could be a risk factor to increase in blood pressure.

Objectives Psoriasis is an autoimmune, inflammatory disease that needs a reliable animal model. Imiquimod (IMQ)-induced psoriasis is a widely used preclinical tool for psoriasis research. However, this model is sensitive to the genetic variation of mice. The present study explores mice’s genetic background on disease stability and severity induced by IMQ. Methods Three distinct strains of mice (Balb/c, C57BL/6, and Swiss albino) were divided into four groups (Vaseline, IMQ, IMQ+Clobetasol, and IMQ+Curcumin). Psoriasis area severity index (PASI) score, ear/back skin thickness, body weight alterations, and histopathological examination were employed to analyze disease severity. The spleen index studied the systemic effect. Strain effect on oxidative stress induced by IMQ was evaluated by estimating antioxidant factors, superoxide dismutase (SOD), catalase, and glutathione (GSH). Results IMQ application resulted in increased PASI score, thickness, and alterations in body weight, confirming disease development in all the mice. However, the disease stability/severity between these strains was not identical. Although IMQ application caused splenomegaly, IMQ+curcumin treated C57BL/6 mice demonstrated a synergistic effect of IMQ and curcumin on the spleen resulting in increased splenomegaly. Decreased cellular enzyme activity in SOD, Catalase, and levels of GSH was observed in IMQ challenged mice, indicating the participation of the redox system in the genesis of the disease that was comparable among the strains. Conclusions These results indicate the existence of strain-dependent development of the disease. The Swiss model was found to be better in terms of disease severity and stability than other models. Further, a detailed mechanistic study might help to explain the pathological difference between these strains.

Objectives Curcumin is described as an antioxidant, hepato-protective and antifibrotic in liver fibrosis, although its mechanism is still not known. One of the models of the chronic liver disease stemming from oxidative stress and the generation of free radical has been considered to be bile duct ligation (BDL). Paraoxonase 1 (PON1) is a prominent antioxidant enzyme. Therefore, the objective of the present research is to assess the effects of curcumin on upregulation of PON1 in BDL rats. Methods As predicted, the rats have been divided into the four groups of Sham, Sham + Cur (curcumin), BDL and BDL + Cur. We evaluated the efficacy of curcumin (100 mg/kg/day) on protein and gene expression of PON1 and regulatory genes contributed to the gene expression PON1 such as Sp1, PKC α , SREBP-2, AhR, JNK and regulation PON1 activity gene expression of Apo A1. Results Curcumin attenuated alterations in liver histology, hepatic enzymes and the mRNA expression of fibrotic markers (p<0.05). In addition, curcumin increased significantly mRNA, protein expression of PON1 and mRNA of the genes that are contributed to the expression of PON1 such as Sp1, PKC α , SREBP-2, AhR, JNK and increased PON1 activity through upregulation of Apo A1 (p<0.05). Conclusions Cirrhosis progression may be inhibited by treatment with curcumin through the increased influence the expression and activity of PON1.

Objectives Nanotechnology is an exciting field for investigators. Green zinc oxide nanoparticles (ZnO NPs) with Camellia sinensis extract complex are proved to be used in the treatment of the toxicity of monosodium glutamate (MSG) in the liver, kidney, and testis of rats. Therefore, the synthesized complex of green nanoparticles using green tea extract (GTE) was tested against the toxicity of MSG on the pancreas. Methods The glucose and insulin levels were estimated as well as some biochemical parameters for evaluating the antioxidant status of the pancreas tissue. The histopathological change of the pancreas also has been determined. Results It indicates the biomedical capability of ZnO NPs/GTE to act as potent antidiabetic through decreasing blood glucose and increasing serum insulin also, inhibition of lipid peroxidation and enhancement of the antioxidant parameters. Conclusions The ZnO NPs/GTE enhanced the pancreatic cell and Langerhans islets as well lowered the sugar levels and stimulated insulin.

Objectives Rauvolfia vomitoria is a medicinal plant used traditionally in Africa in the management of several human diseases including psychosis. However, there is inadequate scientific information on the potency of the phenolic constituents of R. vomitoria leaf in the management of neurodegeneration. Therefore, this study characterized the phenolic constituents and investigated the effects of aqueous and methanolic extracts of R. vomitoria leaf on free radicals, Fe 2+ -induced lipid peroxidation, and critical enzymes linked to neurodegeneration in rat’s brain in vitro . Methods The polyphenols were evaluated by characterizing phenolic constituents using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The antioxidant properties were assessed through the extracts ability to reduce Fe 3+ to Fe 2+ ; inhibit ABTS, DPPH, and OH radicals and Fe 2+ -induced lipid peroxidation. The effects of the extracts on AChE and MAO were also evaluated. Results The phenolic characterization of R. vomitoria leaf revealed that there were more flavonoids present. Both aqueous and methanolic extracts of R. vomitoria leaf had inhibitory effects with the methanolic extract having higher significant (p≤0.05) free radicals scavenging ability coupled with inhibition of monoamine oxidases. However, there was no significant (p≤0.05) difference obtained in the inhibition of lipid peroxidation and cholinesterases. Conclusion This study suggests that the rich phenolic constituents of R. vomitoria leaf might contribute to the observed antioxidative and neuroprotective effects. The methanolic extract was more potent than the aqueous extract; therefore, extraction of R. vomitoria leaf with methanol could offer better health-promoting effects in neurodegenerative condition.

Objectives Exposure to cadmium (Cd), which causes environmental and industrial pollution, causes toxicity in many tissues and organs, especially bone, lung and kidney. Hormones, growth factors and other stimuli act on bone tissue through osteoblasts. In this study, it was aimed to determine the effects of Cd on hFOB1.19 osteoblast cells and the protective and healing potentials of estrogen, androgen and vitamin D against the inhibitory effect of Cd on the proliferation. Methods hFOB1.19 cells were cultivated in our laboratory using Dulbecco’s Modified Eagle’s Medium-F12, HEPES medium, containing 10% fetal bovine serum, 1% penicillin/streptomycin in 34.5 °C 5%CO2 incubator. To determine its protective potentials for the toxicity of CdCl 2 , it was previously applied 1,25(OH) 2D vitamin, 17 β -estradiol, and 5 α -androstane for 72 h to cells. To determine their curative potential, osteoblast cells, which were previously exposed to CdCl 2 for 72 h, were administered 1,25(OH) 2D vitamin, 17 β -estradiol, and 5 α -androstane. Following these applications were determined proliferation by XTT analysis and, the amounts of androgen receptor, estrogen receptor, vitamin D receptor, alkaline phosphatase, osteocalcin and osteoprotegerin by ELISA analysis. Results Vitamin D has been both preventive and curative effective to increase cell proliferation, which Cd reduces. Interestingly, estrogen had a preventive effect and androgen had a curative effect. Conclusions In addition to showing the negative effects of cadmium on the proliferation of osteoblast cells, this study provides an overview of the effects of hormone and vitamin D applications before and after Cd, and these results may serve as a guide for future studies.

Objectives Methotrexate (MTX) is an anticancer drug used in chemotherapy. MTX was known for its toxic effects involving most of the organs including testis. Bee pollen is healthy food for human and has antioxidant effect. We intended to determine protective effect of bee pollen against testicular injury caused by MTX in rats. Methods Thirty-two adult Sprague Dawley male rats were used, and 4 groups were formed: control, MTX, pollen, and MTX + pollen. Rats were given pollen at a dose of 400 mg/kg with intragastric gavage for 10 days. On day 7, MTX was administered a single dose of 30 mg/kg ip. Serum testosterone and LH, tissue MDA level, and SOD and CAT enzyme activities were examined. In addition, spermatological parameters were evaluated. Results MDA level and SOD activity increased while testosterone level decreased significantly in the MTX group compared to the control group. In the MTX + pollen group, MDA level and SOD activity decreased while testosterone level increased. There was no significant change in CAT activity and LH values. Abnormal sperm ratio decreased in the MTX + pollen group compared to the MTX group. Conclusions Our results suggest that bee pollen has a healing effect on reproductive parameters in testicular damage caused by MTX.

Objectives Thousands of food additives are being used by the food industries in ready to eat packed food. These food additives act as either preservatives or enhancers of palatability. Monosodium glutamate (MSG), a sodium salt of glutamic acid is a widely used food additive for enhancing taste. It gives the unique taste to the food called “Umami” or “Savory taste”, which is different from four primary tastes namely, sweet, sour, salty, and bitter. The current experimental study was investigated by dose-related effects of MSG on adult Wistar rats using histological and histomorphometric techniques. Methods Twenty-eight adult Wistar rats were divided into four groups i.e.; one control and three experimental groups. Rats were administered orally with different doses of MSG to the experimental groups and distilled water to the control groups consecutively for 45 days. At the end of the study, rats were sacrificed and tissues were collected for the examination. Results Histomorphometric data of the nuclei diameter of hepatocytes showed significant variation between control and experimental groups. Less PAS-positive material found in a higher dose of MSG-induced rats in histochemical observation. Conclusions One of the challenges of the problem of animal experimental studies is the application of results to human dietary intake of MSG. Based on the dose-dependent findings of the current study; it is evident that the administration of MSG is hepatotoxic in adult Wistar rats.

Background Sericin is a widely used protein in the pharmaceutical industry derived from the silkworm, Bombyx mori , and used for the treatment of various diseases and pathological conditions. It is the main ingredient of the Unani preparation khameera abresham. The study was conducted to evaluate the preclinical toxicity of the silk protein sericin in mice. Methods In the acute toxicity study, sericin was administered once orally to different groups of animals at doses of 500, 1000, and 2000 mg/kg. Animals were observed for 14 days. In the sub-acute toxicity study, sericin was administered in mice for 4 weeks in the toxic group at doses of 500, 1000, and 2000 mg/kg, while in the recovery group it was administered for 4 weeks at doses of 500 and 2000 mg/kg followed by 2 weeks of distilled water administration. Results In the acute toxicity study, the observed parameters showed no significant difference, and no mortality was reported. In the sub-acute toxicity study, there were no toxicological effects in any of the estimated parameters, while histopathological analysis showed inflammation in vital organs at the dose of 2000 mg/kg. Conclusions Results of our acute toxicity study suggest that sericin is safe at all administered doses, while the sub-acute study suggests that the NOAEL (no-observed-adverse-effect level) of sericin is below 2000 mg/kg, at which it can be considered safe.