Beneficial effect of metformin on tolerance to analgesic effects of sodium salicylate in male rats.

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

Pain-Insomnia-Depression Syndrome: Triangular Relationships, Pathobiological Correlations, Current Treatment Modalities, and Future Direction.

Pain-insomnia-depression syndrome (PIDS) is a complex triad of chronic pain, insomnia, and depression that has profound effects on an individual's quality of life and mental health. The pathobiological context of PIDS involves complex neurobiological and physiological mechanisms, including alterations in neurotransmitter systems and impaired pain processing pathways. The first-line therapeutic approaches for the treatment of chronic pain, depression, and insomnia are a combination of pharmacological and non-pharmacological therapies. In cases where patients do not respond adequately to these treatments, additional interventions such as deep brain stimulation (DBS) may be required. Despite advances in understanding and treatment, there are still gaps in knowledge that need to be addressed. To improve our understanding, future research should focus on conducting longitudinal studies to uncover temporal associations, identify biomarkers and genetic markers associated with PIDS, examine the influence of psychosocial factors on treatment responses, and develop innovative interventions that address the complex nature of PIDS. The aim of this study is to provide a comprehensive overview of these components and to discuss their underlying pathobiological relationships.

A rare case report of orchiopexy and hysterectomy in an Afghan boy with persistent Müllerian duct syndrome.

INTRODUCTION: Persistent Müllerian duct syndrome (PMDS), a rare genetic aberration, is characterized by the presence of Müllerian duct (MD) features in males. PMDS is usually caused by a defect in the Müllerian inhibitory system and is discovered during surgical interventions. CASE REPORT: We present the case of a 14-year-old Afghan boy with severe abdominal pain who was initially diagnosed with bilateral undescended testicles and abdominal complex cysts. He was supposed to undergo a cystectomy and orchiopexy surgery. During the surgical intervention, an unexpected finding was made whereby fibrotic-like ovaries, fallopian tubes, and a segment of the uterus were identified, ultimately leading to the diagnosis of PMDS. The MD was carefully removed, and the testicles were delicately repositioned during an orchiopexy procedure. DISCUSSION: In our case, the patient exhibited bilateral undescended testicles along with fibrotic-like ovaries, fallopian tubes, and a portion of the uterus, representing the presence of the female type of PMDS. To safeguard fertility, orchidopexy is recommended for pediatric patients. Conversely, in the older age group, orchidectomy is advised as a precautionary measure against the heightened susceptibility to testicular carcinoma. CONCLUSION: PMDS can be associated with an undescended testicle and abdominal pain. Hence, it is crucial to thoroughly evaluate patients who have undescended testes for the presence of PMDS, and surgeons must maintain a heightened sense of awareness for PMDS while exploring individuals who present with bilateral undescended testes, as exemplified in our case.

Vitamin B12 administration prevents ethanol-induced learning and memory impairment through re-establishment of the brain oxidant/antioxidant balance, enhancement of BDNF and suppression of GFAP.

There are growing evidence indicating that the adolescent brain is persistently affected by the use of psychostimulant agents. In this regard, alcohol drinking has become rather common among the adolescents in many societies during the last decade. It is currently well known that long-term ethanol exposure deteriorates various cognitive functions such as learning and memory. Mechanistically, these adverse effects have been shown to be mediated by oxidative damage to central nervous system. On the other hand, Vit-B12 is known to improve cognitive performance by suppression of oxidative parameters. Thus, in the present study we aimed to test whether treatment by Vit-B12 could prevent ethanol-induced complications in mice using behavioral and biochemical methods. Different groups of male Syrian mice received ethanol, ethanol+Vit-B12, Vit-B12 alone, or saline during adolescence and then learning and memory functions were assessed by Morris water maze (MWM) and Passive Avoidance (PA) tests. Finally, mice were sacrificed for measurement of biochemical factors. Results indicated that, adolescent ethanol intake impairs learning and memory function through exacerbation of oxidative stress and Vit-B12 treatment improves these complications by re-establishment of oxidant/anti-oxidant balance in CNS. Moreover, we found that Vit-B12 prevents ethanol-induced reduction of BDNF and enhancement of GFAP and acetylcholinesterase (AChE) activity. In conclusion, it seems that Vit-B12 supplementation could be used as an effective therapeutic strategy to prevent learning and memory defects induced by chronic alcohol intake during adolescence.