Wide Excision in Hidradenitis Suppurativa. Does it Modify the Course of Disease?

There is a lack of studies assessing whether wide excision surgery in hidradenitis suppurativa affected areas is useful for the global control of the hidradenitis suppurativa. We aimed to find whether surgery results were a better global control on the disease activity in both, the area where the surgery is performed and distant areas. We evaluated the disease course of 17 patients with hidradenitis suppurativa who underwent wide excision of complex fistula tracts between October 2018 and January 2022 at the Hospital Universitario de la Princesa, Madrid. We found that wide excision of complex fistulas produces an overall positive effect on the inflammatory activity in hidradenitis suppurativa that may be important to achieve an adequate control of the disease.

High-fat diet feeding induces a depot-dependent response on the pro-inflammatory state and mitochondrial function of gonadal white adipose tissue.

Obesity has been related to a chronic pro-inflammatory state affecting white adipose tissue (WAT), which has a great impact on carbohydrate, lipid and energy metabolism. In turn, the dysregulation of adipokine secretion derived from the accumulation of excess lipids in adipocytes further contributes to the development of insulin resistance and can be associated with mitochondrial dysfunction. The aim of the present study was to determine whether sexual dimorphism found in the systemic insulin sensitivity profile is related to sex differences in a high-fat diet (HFD) response of gonadal WAT at mitochondrial function and inflammatory profile levels. Wistar rats (10 weeks old) of both sexes were fed a control pelleted diet (3 % (w/w) fat; n 8 for each sex) or a HFD (24 % (w/w) fat; n 8 for each sex). Serum insulin sensitivity markers, mRNA expression levels of inflammatory factors and the protein content of insulin and adiponectin signalling pathways were analysed, as well as the levels of the main markers of mitochondrial biogenesis, antioxidant defence and oxidative damage. In the present study, the periovarian depot exhibits a greater expandability capacity, along with a lower hypoxic and pro-inflammatory state, without signs of mitochondrial dysfunction or changes in its dynamics. In contrast, epididymal fat has a much more pronounced pro-inflammatory, hypoxic and insulin-resistant profile accompanied by changes in mitochondrial dynamics, probably associated with HFD-induced mitochondrial dysfunction. Thus, this explains the worse serum insulin sensitivity profile of male rats.

Sex-dependent differences in rat brown adipose tissue mitochondrial biogenesis and insulin signaling parameters in response to an obesogenic diet.

Marked sex-dependent differences in mitochondrial function and redox status have been found in brown adipose tissue (BAT) of control rats. Insulin also plays a role in the development and maintenance of this tissue. The aim was to investigate sexual dimorphism in the effects of diet-induced obesity on BAT mitochondrial function, as well as on insulin signaling pathway. 10-week-old Wistar rats of both sexes were fed a control diet or a palatable high-fat diet for 26 weeks. Serum markers of insulin sensitivity were analyzed. Mitochondrial DNA (mtDNA) content, mitochondrial oxidative activities, PGC-1α mRNA levels, as well as the protein levels of insulin receptor subunit ß (IRß), glucose transporter GLUT4, ß(3)-adrenergic receptor (ß(3)-AR), phosphatidylinositol 3-kinase, mitochondrial transcription factor A (TFAM), cytochrome c oxidase subunit IV (COX IV), and uncoupling protein 1 (UCP1) were measured in BAT. Obese females showed impaired systemic insulin sensitivity accompanied by diminished IRß, GLUT4, and ß(3)-AR protein levels in BAT. In addition, TFAM and COX IV protein and PGC-1α mRNA levels decreased in obese females, whereas mtDNA levels increased. In obese males, oxidative and thermogenic capacities rose and no significant changes were observed in the insulin signaling pathway elements. The reduction of the insulin signaling pathway in BAT of obese females may be responsible, at least partially, for the impaired biogenesis process, which could favor the increase of body weight found in this sex. In contrast, the enhanced mitochondrial functionality in the BAT of males would avoid increased oxidative damage and the impairment of insulin signaling.

Rat visceral yolk sac (VYS) and placenta mitochondrial features during the placentation period.

The transference of the nutritional function from the VYS to the chorioallantoic placenta during middle pregnancy is a key event for the activation of embryo oxidative metabolism. However, the metabolic adaptations occurring in these tissues during this critical period have not been studied to date. Herein, we investigate the VYS and placenta mitochondrial adaptations throughout gestational days 11, 12 and 13. The results reflect that, during the placentation period, mitochondrial proliferation predominates over differentiation in placenta. Besides, VYS development and mitochondriogenesis show a slowdown despite maintaining the mitochondrial OXPHOS capacities, hence becoming a supporting tissue until the placenta functions are completely available.

Mitochondrial differentiation and oxidative phosphorylation system capacity in rat embryo during placentation period.

Mitochondrial biogenesis and function are essential for proper embryo development; however, these processes have not been further studied during the placentation period, when important oxidative metabolism activation is taking place. Thus, the aim of the present study was to investigate the oxidative phosphorylation system (OXPHOS) enzymatic activities as well as the expression of genes involved in the coordinated regulation of both mitochondrial and nuclear genomes (peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factors 1 and 2, mitochondrial single-strand DNA-binding protein, mitochondrial transcription factor A), and mitochondrial function (cytochrome c oxidase subunit IV, cytochrome c oxidase subunit I and beta-ATP phosphohydrolase) in rat embryo throughout the placentation period (gestational days 11, 12 and 13). Our results reflect that embryo mitochondria were enhancing their OXPHOS potential capacities, pointing out that embryo mitochondria become more differentiated during the placentation period. Besides, the current findings show that the mRNAs of the nuclear genes involved in mitochondrial biogenesis were downregulated, whereas their protein content together with the mitochondrial DNA expression were upregulated throughout the period studied. These data indicate that the molecular regulation of the mitochondrial differentiation process during placentation involves a post-transcriptional activation of the nuclear-encoded genes that would lead to an increase in both the nuclear- and mitochondrial-encoded proteins responsible for the mitochondrial biogenic process. As a result, embryo mitochondria would reach a more differentiated stage with a more efficient oxidative metabolism that would facilitate the important embryo growth during the second half of the pregnancy.

Responses of mitochondrial biogenesis and function to maternal diabetes in rat embryo during the placentation period.

Mitochondria are cellular organelles that have been reported to be altered in diabetes, being closely related to its associated complications. Moreover, mitochondrial biogenesis and function are essential for proper embryo development throughout the placentation period, occurring during organogenesis, when a great rate of congenital malformations have been associated with diabetic pregnancy. Thus, the aim of the current work was to investigate the effect of the diabetic environment on mitochondrial function and biogenesis during the placentation period. For this purpose, we studied the oxidative phosphorylation system (OXPHOS) enzymatic activities as well as the expression of genes involved in the coordinated regulation of both mitochondrial and nuclear genome (PGC-1alpha, NRF-1, NRF-2alpha, mtSSB, and TFAM) and mitochondrial function (COX-IV, COX-I, and beta-ATPase) in rat embryos from control and streptozotocin-induced diabetic mothers. Our results reflected that diabetic pregnancy retarded and altered embryo growth. The embryos from diabetic mothers showing normal morphology presented a reduced content of proteins regulated through the PGC-1alpha mitochondriogenic pathway on gestational day 12. This fact was accompanied by several responses that entailed the activation of OXPHOS activities on the same day and the recovery of the content of the studied proteins to control levels on day 13. As a result, the mitochondria of these embryos would reach a situation close to control on day 13 that could allow them to follow the normal mitochondriogenic schedule throughout a gestational period in which the mitochondrial differentiation process is critical. Nevertheless, malformed embryos from diabetic mothers seemed to show a lower adaptation capability, which could exacerbate their maldevelopment.

Gender- and site-related effects on lipolytic capacity of rat white adipose tissue.

Gender- and site-related differences in the lipolytic capacity, at the different steps of the adrenergic pathway, in gonadal and inguinal white adipose tissue (WAT), were assessed by studying alpha2A-adrenergic receptor (AR), beta3-AR and hormone-sensitive lipase (HSL) protein levels, and by determining the lipolytic response to different agents. Gonadal WAT showed a lower alpha2A/beta3-AR ratio, a greater lipolytic capacity in response to AR agonists, and higher HSL activity and protein levels than inguinal WAT. In female rats, we found greater alpha2A-AR protein levels and alpha2A/beta3-AR ratio compared to their male counterparts, but, on the other hand, a higher lipolytic response to beta-AR agonists and a greater lipolytic capacity at the postreceptor level, including a more activated HSL protein. Thus, the lipolytic capacity was clearly higher in gonadal than in inguinal WAT, at the different steps of the adrenergic pathway studied. Moreover, in both tissues, females showed a greater inhibition of lipolysis via alpha2-AR, which was counteracted by the higher lipolytic capacity at the postreceptor level.

Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects.

The aim of this study was to identify candidate genes for visceral obesity by screening for genes strongly differentially expressed between human subcutaneous and visceral adipose depots. A cDNA microarray with human adipose-derived cDNAs was used as an initial screening to identify genes that are potentially differentially expressed between human subcutaneous and visceral abdominal fat tissues. For the two best candidates, carboxypeptidase E (CPE) and thrombospondin-1 (THBS1) (EST N72406), real-time RT-PCR was performed to confirm their depot specific expression in extremely obese individuals. Both genes appeared to be strongly differentially expressed, having a higher expression in the visceral depot than in the subcutaneous one. For THBS1, the difference in expression between the depots was greater in women than in men. The involvement of CPE and THBS1 in obesity allows us to suggest that the physiological processes controlled by these genes contribute to depot and gender-related differences in the metabolic complications of obesity.

Predictors of adverse events after percutaneous transluminal coronary angioplasty in a group of Hispanic patients.

OBJECTIVE: To identify predictors of adverse events after PTCA during hospitalization and after hospital discharge in a private hospital in Puerto Rico. BACKGROUND: A review of the literature shows limited information about predictors of adverse events associated to percutaneous transluminal coronary angioplasty (PTCA) in Hispanic patients. METHODS: This is a non-concurrent prospective study. Baseline variables were analyzed using multivariate logistic regression to identify predictors of adverse events. Data were collected from medical charts and telephone reports from referring physicians. RESULTS: Data from 197 subjects undergoing PTCA were analyzed for this study. Median age of patients was 65 years, and 62.9% of patients were male. Angiographic success rate was 81.6%. A total of 8.1% of patients had at least one in-hospital adverse event, and 39.8% had at least one adverse event after hospital discharge. After multivariate analysis, a statistically significant association was found between the presence of at least one lesion with residual stenosis of 50% or greater and the risk of developing adverse events in-hospital (RO 11.75; 95% CI 4.32-31.97). A marginally significant association was found between family history of heart disease (RO 2.75; 95% CI 0.93-8.11) and the risk of adverse events during hospitalization. Family history of heart disease (RO 1.41; 95% CI 0.98-2.04) and the presence of at least one lesion with residual stenosis of 50% or greater (RO 2.87; 95% CI 0.82-10.01) showed marginally significant associations with increased risk for adverse events after discharge. CONCLUSIONS: These findings suggest that the presence of at least one lesion with residual stenosis of 50% or greater and family history of heart disease may be risk factors for adverse events after PTCA during hospitalization and after discharge.

[Acute kidney failure as the clinical presenting form of renal Burkitt's lymphoma in an HIV-positive patient]. / Fracaso renal agudo como forma de presentación clínica de linfoma de Burkitt renal en un paciente HIV positivo.

Burkitt's lymphoma is a tumour often associated with low immunity as acute lymphoblastic leukaemia (l3) or infection by the human immunodeficiency virus (HIV). The incidence of renal affection is variable (34-62%) and there are different aetiologies. We present a case of acute renal failure in a patient with a Burkitt's lymphoma and renal infiltration, and infected by the human immunodeficiency virus.

Effects of cafeteria diet feeding on beta3-adrenoceptor expression and lipolytic activity in white adipose tissue of male and female rats.

OBJECTIVE: To investigate the effects of short term (15 days) cafeteria diet feeding on the expression of beta3-AR in vivo and its association with lipolytic stimulation induced by beta3-AR agonist CGP12177A in isolated white adipocytes. ANIMALS: Six female and 6 male Wistar rats (at 4 weeks of age) were fed on a cafeteria diet plus standard diet for 15 days. The remaining 12 age- and sex-matched rats always received standard diet only. MEASUREMENTS: White gonadal adipose tissue was isolated and used for the determination of beta3-AR and leptin expression, and for in vitro studies of lipolytic activity. RESULTS: Control male rats had higher levels of both beta3-AR and leptin mRNA in white adipose tissue than their female counterparts. Both male and female rats up-regulated the levels of both beta3-AR and leptin mRNA in response to 15 day cafeteria diet feeding. Noradrenaline- and isoprenaline-induced lipolysis were significantly increased in fat cells from control females compared to their male counterparts. CGP12177A stimulation resulted in significantly higher glycerol release in fat cells from cafeteria diet-fed female rats, whereas there were no differences due to dietary treatment in male rats. The maximal lipolytic response of forskolin (stimulating adenylyl cyclase) and dibutyryl cyclic AMP (cyclic AMP analogous) was not affected by sex or cafeteria diet feeding. CONCLUSION: Cafeteria diet feeding brings about higher excess body weight and impaired adipose tissue lipolytic activity in female rats compared to male rats. Thus, the higher levels of beta3-AR mRNA induced by cafeteria feeding are not indicative per se of an increase of the lipolytic response of the adipocytes. The changes seen in other adrenoceptor subtypes (beta1 and beta2) may be more determinant of the overall lipolytic response of adipocytes.

Effects of fasting on lipoprotein lipase activity in different depots of white and brown adipose tissues in diet-induced overweight rats.

The aim of the present study was to evaluate the effects of 24 hours of starvation on lipoprotein lipase (LPL) activity in various depots of white and brown adipose tissues in control rats and in rats with two different degrees of overweight, both induced by dietary treatment. In control rats, no changes in LPL immunoreactive mass were observed in either white or brown adipose tissues after fasting, whereas the effects of food deprivation on enzyme activity were opposite in white versus brown adipose tissues. The LPL activity response to fasting was impaired by obesity: White adipose depots of cafeteria obese rats showed a lower ability to downregulate LPL during fasting and the increased LPL activity induced by fasting in brown adipose depots was less intense in the obese rats compared with control animals. When the degree of overweight was reduced, the differences between obese and control rats were also attenuated.

Hepatic glycogen and lactate handling in dietary obese rats.

Hepatic balances for glucose and its precursor, lactate, were calculated by measuring hepatic blood flows and the arteriovenous differences of these metabolites in 2 groups of overweight rats: cafeteria diet-fed rats and post-cafeteria rats. Obese rats show abnormal hepatic glycogen handling, since they do not mobilize all hepatic glycogen stores after 24-hour starvation, in a situation in which a lower rate of hepatic glucose output and a higher capacity for lactate uptake are attained. The important decrease (about 50%) in the hepatic blood flows observed in post-cafeteria rats versus control rats was similar to that caused by 24-hour starvation in control animals, suggesting that after withdrawal of the cafeteria diet, the liver blood flow of the post-cafeteria rats was adapted to the low-food intake in order to make better use of the energy consumed. The results also suggest an increased efficiency of hepatic lactate uptake in post-cafeteria rats.

Effect of 12, 24 and 72 hours fasting in thermogenic parameters of rat brown adipose tissue mitochondrial subpopulations.

The aim of the present work was to study the effects of various durations of fasting (12, 24 and 72 hours) on brown adipose tissue (BAT) thermogenic parameters--cytrochrome-c-oxidase (COX) activity, GDP-binding activity and uncoupling protein (UCP1) content--and also on morphological features of different mitochondrial subpopulations, obtained by differential centrifugation--M1 (1000 g), M3 (3000 g) and M15 (15,000 g) fractions. The mitochondrial subpopulations showed morphological differences and a different distribution of UCP1 levels and of GDP-binding in all experimental groups. Starvation induced a decrease in the average size for all mitochondrial subtypes. The main changes induced by fasting in thermogenic parameters were observed in the M15 subtype. After the first 24h of starvation, there was a significant decrease of UCP1 levels only in the lightest mitochondrial subpopulation. However, the 72h fasted situation reflected a tendency to increase UCP1 content and UCP1/COX ratio together with a significant decrease of GDP-binding/UCP1 ratio, thus indicating more masked GDP-binding sites. Important fasting-induced changes in both morphological and biochemical parameters in BAT mitochondrial subtypes reflect their role in the physiological response of BAT to starvation.

Fatty acid composition of brown adipose tissue in dietary obese rats.

The effects of both dietary obesity and a food deprivation period of 24 hours on fatty acid composition of brown adipose tissue have been investigated. Long time exposure to a hypercaloric high-fat diet such as the cafeteria diet induced an important tissue fatty acid accumulation, mainly for the major saturated and monounsaturated fatty acids. Notable metabolic differences have been observed in the behaviour of control and obese rats facing a food deprivation period: a preferential utilization of the most abundant saturated fatty acids in control rats and a minor response in obese rats, with a greater fat accumulation in the interscapular brown adipose tissue.

Changes in fatty acid composition in rat adipose tissue induced by dietary obesity.

The aim of the study was to evaluate the effects of cafeteria feeding on the composition of fatty acids in retroperitoneal fat pad and also to determine what happens to fatty acids when rats previously fed the cafeteria diet are returned to regular rat chow. The study of the post-cafeteria rats enabled us to determine the effects of dietary induced excess weight in the absence of artefactual interferences from the diet because these rats, unlike the cafeteria obese rats, ate the same diet as controls. In response to cafeteria feeding there were increases in the majority of adipose tissue fatty acids. However, significant decreases were observed in the relative proportions of 18:2n-6 and in two related n-6 polyunsaturated fatty acids (18:3n-6 and 20:3n-6), as well as in 16:1. In the post-cafeteria obesity model the previous dietary influence on fatty acid composition was still evident. The maintenance of both the high levels and proportions of 18:1 and the decrease of 16:1 percentage in the post-cafeteria rats argues in favour of an alteration in the activity of the elongation metabolic pathway. Certain changes affecting polyunsaturated fatty acid adipose depot composition of obese rats, mainly the decreased levels of 18:2n-6, are long lasting and could be related to the maintenance of the obese status. On the whole, although the fatty acid composition of adipose tissue is influenced by the composition of the diet, there are some differences in both the maintenance of the effects and also in the selectivity of adipose tissue for the different fatty acids of obese and lean rats.

Protein and amino acid intake in cafeteria fed obese rats.

Food selection pattern and portal blood amino acid profile were examined in rats given a cafeteria diet. Compared to standard-diet fed rats, cafeteria-diet fed rats consumed more energy. Increase in energy intake was attributable to an increase in fat intake. Protein intake was slightly higher and carbohydrate intake remained constant and was similar to levels consumed by standard-diet fed rats. The cafeteria rats took up higher quantities of Phenylalanine+Tyrosine, Arginine, Histidine, Lysine, Leucine, Isoleucine, Valine, Threonine, and Glycine, lower quantities of Tryptophan and the same quantity of Methionine+Cysteine vs. control rats. Portal concentrations of Serine, Threonine, Tryptophan and Lysine were significantly higher in cafeteria-diet fed rats than in standard-diet fed rats. This can be interpreted in such a way that, on the whole, the quality of protein ingested by cafeteria and control rats is similar. No statistical differences in the ingestion of individual amino acids were observed between different days of the period of cafeteria diet feeding, thus the idea of a strict control of protein ingestion irrespective of the obese status is reinforced.

Blood cell to plasma gradients of amino acids in arterial and venous blood in fed and fasted rats.

Measurement of amino acid concentrations in blood cells and plasma, and the calculated blood cell to plasma gradients (C/P) from both afferent and efferent vessels to tissues, allowed evaluation of the effect of several tissues (splanchnic bed, skeletal muscle and kidney) on blood amino acid distribution in fed and starved rats. Combined effects of tissues and erythrocyte transport capabilities determined specific C/P values for each amino acid. For amino acids related to the L-system, the high capacity of this erythrocyte transport many buffer some C/P changes as an effect of tissue metabolism. For less permeable amino acids (like Asp and Glu) plasma changes were mainly responsible for changes in C/P values, whereas for other amino acids (such as basic amino acids) blood cells became the main determinants of C/P changes, mainly in starvation. In general, the role of erythrocytes in amino acid transport was enhanced in starvation.