The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concems due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and phar-maceutical excipients,along with novel analytical strategies for detection,root cause analysis,refor-mulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This compre-hensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

The etiology of recurrent miscarriage (RM) is extremely heterogeneous, encompassing genetic, immunological, anatomical, endocrine, thrombophilic, infectious, and uterine abnormalities. Thrombophilia is a major contributor to pregnancy complications, potentially harming the fetus and jeopardizing the continuation of pregnancy. Therefore, successful pregnancy outcomes depend on maintaining a delicate balance between coagulation and fibrinolytic factors, crucial for ensuring the adjustment of the basal plate to facilitate adequate placental perfusion. Despite numerous studies shedding light on the role of thrombophilic factors and genetic variations in RM, the exact pathogenesis remains unclear. It is imperative to systematically rule out thrombophilia and other related factors responsible for pregnancy disorders and RMs to guide appropriate and active management strategies. Addressing thrombophilia continues to present challenges in terms of effective treatment. The current review aims to address the heterogeneity of RM as a therapeutic challenge, emphasizing the need for standardized diagnostic tests and welldesigned multicenter research trials to gather robust, evidence-based data on thrombophilic causes of RM and provide effective treatment. The goal is to enhance the understanding of thrombophilic factors and genetic landscapes associated with RM through various approaches, including candidate gene studies, genome-wide association studies, and high-throughput sequencing. Meta-analyses have underscored the significance of genetic aberrations in RM, highlighting the necessity for identifying critical mutations implicated in the etiopathogenesis of miscarriages to pave the way for implementation of targeted clinical therapies.

Objective: Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. Methods: Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. Results: Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. Conclusion Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

Networks of synaptically connected neurons underlie all brain functions. Various cell-cell signaling and extrinsic molecules influence synapse assembly at the synaptic site. Calcium ions play a significant role in signal transduction pathways that control various neuronal functions. Multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMK II) is an important mediator of calcium signaling in neurons, it plays an essential role in controlling synaptic strength and plasticity, and it is highly expressed in the cytosol of developing neurons, especially in presynaptic neurons. However, the precise role of CaMKII in synapse formation and synaptic transmission has not yet been determined. We hypothesized that CaMKII activity could be necessary for synapse formation and synaptic transmission. To test whether CaMKII activity is required for the synapse formation and synaptic transmission, the identified neurons visceral dorsal 4 (VD4 – presynaptic) and its postsynaptic partner left pedal dorsal 1 (LPeD1) from the freshwater snail Lymnaea stagnalis were paired in soma-soma configuration in cell culture. The soma-soma paired cells recapitulated their excitatory connections in vitro. To test the possible role of CaMKII in synapse formation and synaptic transmission, the in vitro paired neurons were exposed to a CaMKII-specific inhibitor KN-93 and its inactive analog KN-92. The incidence of synapse formation and efficacy of synaptic transmission was tested electrophysiologically.

BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
Animals ; Biomarkers ; Endocrine Disruptors/toxicity* ; Environmental Exposure/adverse effects* ; Environmental Pollutants/toxicity* ; Hypothalamo-Hypophyseal System/physiopathology* ; Infertility, Male/physiopathology* ; Male ; Phenols/toxicity* ; Rats ; Rats, Sprague-Dawley ; Sulfones/toxicity* ; Testis/physiopathology* ; Toxicity Tests, Chronic

Purpose: Many studies have shown that the enhanced recovery after surgery (ERAS) protocols improve postoperative surgical outcomes. The purpose of this study was to observe the effects on postoperative inflammatory markers and to explore the effects of a high degree of compliance and the use of epidural anesthesia on inflammation and surgical outcomes. Methods: Four hundred patients underwent colorectal cancer surgery at 2 hospitals during 2 different periods, namely, from January 2006 to December 2009 and from January 2017 to July 2017. Data related to the patient’s clinicopathological features, inflammatory markers, percentage of compliance with elements of the ERAS protocol, and use of epidural anesthesia were collected from a prospectively maintained database. Results: The complication rate and the length of hospital stay (LOS) were less in the ERAS group than in the conventional group (P = 0.005 and P ≤ 0.001, respectively). The postoperative white blood cell count and the duration required for leukocytes to normalize were reduced in patients following the ERAS protocol (P ≤ 0.001). Other inflammatory markers, such as lymphocyte count (P = 0.008), neutrophil/lymphocyte ratio (P = 0.032), and C-reactive protein level (P ≤ 0.001), were lower in the ERAS protocol group. High compliance ( ≥ 70%) was strongly associated with the complication rate and the LOS (P = 0.008 and P ≤ 0.001, respectively). Conclusion ERAS protocols decrease early postoperative inflammation and improves short-term postoperative recovery outcomes such as complication rate and the LOS. High compliance ( ≥ 70%) with the ERAS protocol elements accelerates the positive effects of ERAS on surgical outcomes; however, the effect on inflammation was very small.