Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis.

BACKGROUND: Adipose-derived stem cells (ADSC) are multipotent cells implicated in tissue homeostasis. Obesity represents a chronic inflammatory disease associated with metabolic dysfunction and age-related mechanisms, with progressive accumulation of senescent cells and compromised ADSC function. In this study, we aimed to explore mechanisms associated with the inflammatory environment present in obesity in modulating ADSC to a senescent phenotype. We evaluated phenotypic and functional alterations through 18 days of treatment. ADSC were cultivated with a conditioned medium supplemented with a pool of plasma from eutrophic individuals (PE, n = 15) or with obesity (PO, n = 14), and compared to the control. RESULTS: Our results showed that PO-treated ADSC exhibited decreased proliferative capacity with G2/M cycle arrest and CDKN1A (p21WAF1/Cip1) up-regulation. We also observed increased senescence-associated ß-galactosidase (SA-ß-gal) activity, which was positively correlated with TRF1 protein expression. After 18 days, ADSC treated with PO showed augmented CDKN2A (p16INK4A) expression, which was accompanied by a cumulative nuclear enlargement. After 10 days, ADSC treated with PO showed an increase in NF-κB phosphorylation, while PE and PO showed an increase in p38MAPK activation. PE and PO treatment also induced an increase in senescence-associated secretory phenotype (SASP) cytokines IL-6 and IL-8. PO-treated cells exhibited decreased metabolic activity, reduced oxygen consumption related to basal respiration, increased mitochondrial depolarization and biomass, and mitochondrial network remodeling, with no superoxide overproduction. Finally, we observed an accumulation of lipid droplets in PO-treated ADSC, implying an adaptive cellular mechanism induced by the obesogenic stimuli. CONCLUSIONS: Taken together, our data suggest that the inflammatory environment observed in obesity induces a senescent phenotype associated with p38MAPK/NF-κB axis, which stimulates and amplifies the SASP and is associated with impaired mitochondrial homeostasis.

Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review.

Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity. This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity. This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation. The studies differed in their methodologies as well as their intervention lengths. Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp. and Bifidobacterium sp. The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time. Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat. Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes. All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss. These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon. In contrast, prebiotics might restore a healthy microbiome and reduce body fat.

Metabolic surgery for the treatment of type 2 diabetes in pancreas after kidney transplant candidates.

Metabolic surgery for the treatment of type 2 diabetes mellitus (T2DM) in patients not morbidly obese (BMI <35) has been widely studied. Taking into account that ∼12% of pancreas transplants are performed in patients with T2DM, our goal was to evaluate the impact of metabolic surgery on the management of obese patients with T2DM on waiting lists for a pancreas transplant. We performed a Roux-en-Y gastrointestinal bypass in 5 patients with insulin-dependent T2DM who were candidates for pancreas after kidney transplant and with a BMI <35. Three patients became insulin independent by the end of the first year while the other 2 reduced their insulin requirements by 70%. Furthermore, all patients achieved improved control of lipid levels. We concluded that the surgery was effective in controlling blood glucose and lipid metabolism in these obese T2DM kidney transplant recipients. In this population, a pancreas transplant, along with its associated morbidity, may be avoided.

Functioning of obese individuals in pre- and postoperative periods of bariatric surgery.

BACKGROUND: Obesity is a pathologic condition that causes functional incapacity, with reduction of quality of life and life expectancy and an increase in mortality. Bariatric surgery is indicated to alleviate associated comorbidities and increase physical capacity. The objective of this work was to evaluate the functional capacity of patients with morbid obesity before and after (3 months) bariatric surgery. METHODS: This was a cross-sectional study involving 67 patients, where 61 were women and six men, with a mean age of 38 ± 10 years and mean BMI of 50.45 ± 8.5 kg/m2. All patients were assessed before surgery and 3 months afterwards. The following assessments were performed: 6-min walk test (6MWT), functional independence measure (FIM), and test for risk of falling and transfer capacity, called the timed up-and-go test. RESULTS: The study demonstrated a reduction in parameters evaluated in 6MWT with a statistically significant difference at two times (rest and final) when evaluated before and after bariatric surgery (p < 0.001). In relation to the FIM and timed up-and-go test, the patients showed a statistically significant improvement (p < 0.001) for both when comparing the tasks evaluated at the pre- and postoperative moments. CONCLUSIONS: Obesity has an impact on the functioning and quality of life of patients. We observed an improvement in all instruments used for assessment before and after bariatric surgery, where a linear component was demonstrated in relation to diminution of body mass index and functioning.

Economic benefits of bariatric surgery.

With the high prevalence of obesity and associated comorbidities, the costs of health services produce a great economic impact. The objective of this work was to evaluate the economic benefits of bariatric surgery and to relate the costs to the impact on the health of the individual. A historic cohort study was conducted, with review of medical charts of 194 patients who fulfilled the inclusion criteria for the study. The costs for medications, professional care, and examinations in the pre- and postoperative periods were analyzed, taking into consideration the comorbidities DM2, SAH, and dyslipidemia. The study demonstrated a reduction in the medical costs in the course of the postoperative period, in relation to expenses for medications, professional care, and examinations in the preoperative period. Comparing the preoperative expenses with different times in the postoperative period, a statistically significant difference was seen at all time evaluated (p < 0.001). The resolution of comorbidities was higher than 95% at 36 months after surgery. No statistically significant difference was seen with respect to the prevalence of comorbidities between the sexes in the pre- and postoperative periods (p > 0.05). With regard to age, younger patients showed lower rates of comorbidities in the pre- and postoperative periods (p < 0.001). The costs of the surgery are high, but the expenditures for medications, professional care, and examinations decrease progressively after the operation, where this is more evident in patients with more associated comorbidities.

Dorsal forearm adipofascial turnover flap among the elderly.

We have assessed the results of soft tissue cover on the back of the hand using an adipofascial turnover flap. From 2004 until 2007, 14 patients (mean age: 62 years) underwent reconstruction of extensive defects in the dorsum of the hand, using a forearm adipofascial turnover flap based on the perforators of the anterior interosseous artery covered with a split skin graft. The pivot point of the flap is typically 4-6 cm proximal to the level of the radial styloid process. In 93% of patients, the reconstruction healed without any problem. The adipofascial turnover flap is a useful and reliable method of reconstruction of the dorsum of the hand even in elderly patients.

A comparison of the use of distal radius vascularised bone graft and non-vascularised iliac crest bone graft in the treatment of non-union of scaphoid fractures.

We compared two surgical techniques for the treatment of scaphoid non-union, namely, using distal radius vascularised bone graft and iliac crest non-vascularised bone graft. Eighty patients with symptomatic scaphoid non-union underwent surgical treatment, including 35 patients treated with distal radius vascularised bone graft and 45 treated by iliac crest non-vascularised bone graft. Patients were assessed objectively by examination of wrist range of motion, grip strength and radiographic findings in the postoperative period after a mean time of 2.8 (1.4) (range 1-5.2) years. Similar functional results were obtained with the two techniques. All cases of non-union in the non-vascularised group obtained consolidation in a mean time of 8.89 (2.26) months and in the vascularised group in a mean time of 7.97 (3.06) months. Three cases of consolidation failure occurred in the vascularised group and were related to technical difficulties.

Can local supply of bone marrow mononuclear cells improve the outcome from late tubular repair of human median and ulnar nerves?

The purpose of this non-randomised retrospective study was to compare nerve regeneration after reconnection with silicone tubes with two different strategies. A total of 44 patients with injured median or ulnar nerves in the forearm were surgically treated. In one group of patients, a silicone tube alone was placed in the nerve gap. In a second group, the silicone tube was filled with autologous bone marrow mononuclear cells obtained by aspiration from the iliac crest. Motor function, sensation and the effect of pain on function were assessed 1 year after surgery. The tubes filled with bone marrow cells showed better recovery than the empty tubes. The use of bone marrow mononuclear cells in addition to tube re-connection may promote better nerve regeneration than conventional tubular repair.

Laparoscopic approach to wandering spleen: a case report and an update to the question.

Wandering spleen is seldom seen in everyday situations, and its prevalence is not well defined in the literature. Its causes are not precisely known, and there is controversy over its management. A 34-year-old woman experienced low-intensity abdominal pain associated with a palpable hypogastric mass, which was confirmed by imaging studies to be a wandering spleen. Because of ureteral compression, a surgical approach was decided upon, and videolaparoscopic splenectomy was chosen. This technique, comments about specific technical issues, and other treatment options presented in the literature are discussed. Videolaparoscopic splenectomy has excellent surgical results, both functional and aesthetic.