Cigarette smoking causes insulin resistance. However, nicotine induces anti-inflammation and improves glucose tolerance in insulin-resistant animal models. Here, we determined the effects of nicotine on glucose metabolism in insulin-sensitive C57BL/J6 mice. Acute nicotine administration (30 min) caused fasting hyperglycemia and lowered insulin sensitivity acutely, which depended on the activation of nicotinic-acetylcholine receptors (nAChRs) and correlated with increased catecholamine secretion, nitric oxide (NO) production, and glycogenolysis. Chlorisondamine, an inhibitor of nAChRs, reduced acute nicotine-induced hyperglycemia. qRT-PCR analysis revealed that the liver and muscle express predominantly β4 > α10 > α3 > α7 and β4 > α10 > β1 > α1 mRNA for nAChR subunits respectively, whereas the adrenal gland expresses β4 > α3 > α7 > α10 mRNA. Chronic nicotine treatment significantly suppressed expression of α3-nAChR (predominant peripheral α-subunit) in liver. Whereas acute nicotine treatment raised plasma norepinephrine (NE) and epinephrine (Epi) levels, chronic nicotine exposure raised only Epi. Acute nicotine treatment raised both basal and glucose-stimulated insulin secretion (GSIS). After chronic nicotine treatment, basal insulin level was elevated, but GSIS after acute saline or nicotine treatment was blunted. Chronic nicotine exposure caused an increased buildup of NO in plasma and liver, leading to decreased glycogen storage, along with a concomitant suppression of Pepck and G6Pase mRNA, thus preventing hyperglycemia. The insulin-sensitizing effect of chronic nicotine was independent of weight loss. Chronic nicotine treatment enhanced PI-3-kinase activities and increased Akt and glycogen synthase kinase (GSK)-3β phosphorylation in an nAChR-dependent manner coupled with decreased cAMP response element-binding protein (CREB) phosphorylation. The latter effects caused suppression of Pepck and G6Pase gene expression. Thus, nicotine causes both insulin resistance and insulin sensitivity depending on the duration of the treatment.
Alcohol consumption appears to be a risk factor for sudden infant death syndrome, although it is unclear whether alcohol is an independent risk factor, a risk factor only in conjunction with other known risk factors (like co-sleeping), or a proxy for other risk factors associated with occasions when alcohol consumption increases (like smoking). Our findings suggest that caretakers and authorities should be informed that alcohol impairs parental capacity and might be a risk factor for sudden infant death syndrome; in addition, future research should further explore possible connections between sudden infant death syndrome and alcohol.
It is estimated that more than 30 million women in the United States are affected by pelvic floor disorders. Of these, 3 million experience pelvic organ prolapse. A robust surgical option for treatment of vaginal vault prolapse is sacrocolpopexy (SC).A rare but life-threatening possible sequela of SC is bowel obstruction. There are only limited data on its prevention, prevalence, detection, and management.Previous studies reported rates of bowel obstruction after SC ranging from 1.9% to 2.5%. A comprehensive review found that bowel obstruction after SC was managed surgically in 0.6%-8.6% of cases. Few studies have described the diagnosis, therapeutic options, and long-term consequences of bowel obstruction. Although early detection and treatment can prevent patient morbidity and mortality from adverse events of obstruction such as bowel incarceration and ischemia, presenting symptoms can be mistakenly attributed to other diagnoses. Especially in the immediate postoperative period, common symptoms of bowel obstruction are often indistinguishable from those of ileus. Bowel obstruction can occur from 5 days to 14 years after surgery, further challenging its diagnosis.The aim of this study was to identify clinical and surgical factors associated with occurrence of bowel obstruction after SC and to describe its presentation, management strategies (medical vs surgical), and long-term sequelae. The authors obtained data from a retrospective case series of patients who underwent open, laparoscopic, or robotic SC between January 1, 2009 and December 31, 2019 at hospitals within a large health maintenance organization and a single academic medical center in Southern California.Of 3231 patients, 32 (1.0%) who underwent SC experienced a subsequent bowel obstruction. Thirteen (40.6%) of the 32 patients underwent SC using an open abdominal approach, and 19 (59.4%) via laparoscopic or robotic approach. Among the 32 patients experiencing bowel obstruction, medical management was undertaken in 19 (59.4%). Of the 13 patients managed surgically, 8 (61.5%) had severe bowel obstruction requiring bowel resection, and 3 (23.1%) had partial mesh excision. Two (10.5%) of the medically managed, and 2 (15.4%) of the surgically managed cases had recurrent obstruction.Findings in this small case series suggest that the type of hysterectomy may not be a risk factor for bowel obstruction. The timing of occurrence of this complication spans from days to nearly a decade after SC, which emphasizes the need for surveillance in the immediate postoperative period as well as long-term. Conservative management may be effective long-term as shown by similar rates of recurrence between medically and surgically managed patients. The data provide information to guide surgeons in patient selection, informed counseling, surgical planning before SC, and may aid in diagnosis and management of bowel obstruction after SC. The study is limited by its small sample size secondary to the low prevalence of bowel obstruction.
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