Anti-inflammatory effect of thalidomide in an experimental lung donor model of brain death.

Lung transplantation stands as a vital treatment for severe lung diseases, primarily sourcing organs from donors with brain death (BD). This research delved into the potential anti-inflammatory effects of thalidomide in rats with BD-induced lung complications. In this study twenty-four Wistar rats were divided into three groups: the control (CTR), brain death (BD) and brain death + thalidomide (TLD) groups. Post specific procedures, a 360 min monitoring period ensued. Comprehensive analyses of blood and heart-lung samples were conducted. Elevated IL-6 levels characterized both BD and TLD groups relative to the CTR (p = 0.0067 and p = 0.0137). Furthermore, TNF-α levels were notably higher in the BD group than both CTR and TLD (p = 0.0152 and p = 0.0495). Additionally, IL-1ß concentrations were significantly pronounced in both BD and TLD compared to CTR, with the BD group surpassing TLD (p = 0.0256). Immunohistochemical assessments revealed augmented NF-ĸB expression in the BD group in comparison to both CTR and TLD (p = 0.0006 and p = 0.0005). With this study we can conclude that BD induced acute pulmonary inflammation, whereas thalidomide manifested a notable capability in diminishing key inflammatory markers, indicating its prospective therapeutic significance in lung transplantation scenarios.

Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death.

INTRODUCTION: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. METHODS: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. RESULTS: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). CONCLUSIONS: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.

Adipocyte-specific Nos2 deletion improves insulin resistance and dyslipidemia through brown fat activation in diet-induced obese mice.

OBJECTIVE: Inducible nitric oxide (NO) synthase (NOS2) is a well-documented inflammatory mediator of insulin resistance in obesity. NOS2 expression is induced in both adipocytes and macrophages within adipose tissue during high-fat (HF)-induced obesity. METHODS: Eight-week-old male mice with adipocyte selective deletion of the Nos2 gene (Nos2AD-KO) and their wildtype littermates (Nos2fl/fl) were subjected to chow or high-fat high-sucrose (HFHS) diet for 10 weeks followed by metabolic phenotyping and determination of brown adipose tissue (BAT) thermogenesis. The direct impact of NO on BAT mitochondrial respiration was also assessed in brown adipocytes. RESULTS: HFHS-fed Nos2AD-KO mice had improved insulin sensitivity as compared to Nos2fl/fl littermates. Nos2AD-KO mice were also protected from HF-induced dyslipidemia and exhibited increased energy expenditure compared with Nos2fl/fl mice. This was linked to the activation of BAT in HFHS-fed Nos2AD-KO mice as shown by increased Ucp1 and Ucp2 gene expression and augmented respiratory capacity of BAT mitochondria. Furthermore, mitochondrial respiration was inhibited by NO, or upon cytokine-induced NOS2 activation, but improved by NOS2 inhibition in brown adipocytes. CONCLUSIONS: These results demonstrate the key role of adipocyte NOS2 in the development of obesity-linked insulin resistance and dyslipidemia, partly through NO-dependent inhibition of BAT mitochondrial bioenergetics.

Direct Conversion of Methane to C2 Hydrocarbons in Solid-State Membrane Reactors at High Temperatures.

Direct conversion of methane to C2 compounds by oxidative and nonoxidative coupling reactions has been intensively studied in the past four decades; however, because these reactions have intrinsic severe thermodynamic constraints, they have not become viable industrially. Recently, with the increasing availability of inexpensive "green electrons" coming from renewable sources, electrochemical technologies are gaining momentum for reactions that have been challenging for more conventional catalysis. Using solid-state membranes to control the reacting species and separate products in a single step is a crucial advantage. Devices using ionic or mixed ionic-electronic conductors can be explored for methane coupling reactions with great potential to increase selectivity. Although these technologies are still in the early scaling stages, they offer a sustainable path for the utilization of methane and benefit from the advances in both solid oxide fuel cells and electrolyzers. This review identifies promising developments for solid-state methane conversion reactors by assessing multifunctional layers with microstructural control; combining solid electrolytes (proton and oxygen ion conductors) with active and selective electrodes/catalysts; applying more efficient reactor designs; understanding the reaction/degradation mechanisms; defining standards for performance evaluation; and carrying techno-economic analysis.

The postnatal window is critical for the development of sex-specific metabolic and gut microbiota outcomes in offspring.

The Developmental Origins of Health and Disease (DOHaD) concept has been proposed to explain the influence of environmental conditions during critical developmental stages on the risk of diseases in adulthood. The aim of this study was to compare the impact of the prenatal vs. postnatal environment on the gut microbiota in dams during the preconception, gestation and lactation periods and their consequences on metabolic outcomes in offspring. Here we used the cross-fostering technique, e.g. the exchange of pups following birth to a foster dam, to decipher the metabolic effects of the intrauterine versus postnatal environmental exposures to a polyphenol-rich cranberry extract (CE). CE administration to high-fat high-sucrose (HFHS)-fed dams improved glucose homeostasis and reduced liver steatosis in association with a shift in the maternal gut microbiota composition. Unexpectedly, we observed that the postnatal environment contributed to metabolic outcomes in female offspring, as revealed by adverse effects on adiposity and glucose metabolism, while no effect was observed in male offspring. In addition to the strong sexual dimorphism, we found a significant influence of the nursing mother on the community structure of the gut microbiota based on α-diversity and ß-diversity indices in offspring. Gut microbiota transplantation (GMT) experiments partly reproduced the observed phenotype in female offspring. Our data support the concept that the postnatal environment represents a critical window to influence future sex-dependent metabolic outcomes in offspring that are causally but partly linked with gut microbiome alterations.

Oral lactate intensifies insulin toxicity during severe insulin-induced hypoglycemia in mice

ABSTRACT We investigated whether oral lactate could prevent seizures and deaths in mice with severe hypoglycemia induced by a high dose of insulin. For this purpose, mice were fasted for 15 h and then given an intraperitoneal injection of regular insulin (5.0 U/kg or 10.0 U/kg). Immediately after insulin injection, the mice received an oral dose of saline (control), glucose (5.5 mmol/kg), or lactate (18.0 mmol/kg). Glucose and lactate levels were measured in the blood and brain before and after the seizures began. Glucose and lactate delayed (p < 0.05) the onset of seizures associated with severe insulin-induced hypoglycemia. Elevated (p < 0.05) brain levels of lactate were associated with an absence of seizures in mice that received glucose or lactate, suggesting that lactate could prevent convulsions associated with severe insulin-induced hypoglycemia. However, the same oral dose of lactate that delayed the onset of convulsions also increased the mortality rate. In contrast, diazepam (3.0 mg/kg) prevented seizures and markedly decreased the frequency of death during severe insulin-induced hypoglycemia. The results demonstrated that in contrast to oral glucose, oral lactate intensifies insulin toxicity.

A polyphenol-rich cranberry extract reverses insulin resistance and hepatic steatosis independently of body weight loss.

OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200 mg/kg, Chow + CE, HFHS + CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS + CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARα) and downregulation of several pro-inflammatory genes (eg, COX2, TNFα) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS + CE mice. The gut microbiota of HFHS + CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

Tratamento da doença de Hailey-Hailey com laser de CO2 fracionado: uma série de três casos / Treatment of the Hailey-Hailey disease with fractional CO2 laser: a three-case series

A doença de Hailey-Hailey ou pênfigo familiar benigno é condição rara, que se caracteriza por lesões vesiculares e erosões, associadas a dor e queimação, que comprometem a qualidade de vida dos pacientes. Existem vários tratamentos tópicos e sistêmicos que podem promover temporariamente a remissão das lesões, não existindo tratamento curativo. Algumas opções de tratamento com resultados duradouros abrangem a dermoabrasão e a vaporização com laser de Erbium YAG ou CO2. Relatamos três casos de pacientes com lesões recorrentes e respostas limitadas aos tratamentos clássicos, que apresentaram melhora clínica importante e alívio sintomático após terapia com laser de CO2 fracionado.

The Hailey-Hailey disease or familial benign pemphigus is a rare condition, characterized by vesicular lesions and erosions with a predilection for intertriginous areas associated with pain and burning sensation that affect the quality of life of patients. There are many topical and systemic treatments for the injuries that can temporarily promote partial or complete remission, but there is no curative treatment. Some treatment options with lasting results include dermabrasion and Erbium laser resurfacing (YAG or CO2). We report three cases of patients with recurrent lesions and limited responses to classical treatments, which showed significant clinical improvement after fractional CO2 laser therapy.

Ocronose exógena tratada com laser de CO2 / Exogenous ochronosis treated with CO2 Laser

Ocronose exógena é doença cutânea rara, geralmente associada ao uso tópico de hidroquinona. Leva à hiperpigmentação acinzentada ou preto-azulada, devido à deposição dérmica de pigmento ocre. Não existe tratamento padronizado, e as opções terapêuticas são em geral frustrantes. Relatamos o caso de uma paciente com ocronose exógena após uso de hidroquinona, tratada com laser fracionado de CO2 e apresentando resultado bastante satisfatório.

Exogenous Ochronosis is a rare skin disease. It is usually associated with the topical use of hydroquinone, resulting in a grayish or bluish black hyperpigmentation due to dermal deposition of ocher pigment. There is no gold standard treatment and the therapeutic options are generally not effective. We report a case of a patient with exogenous achronosis after use of Hydroquinone, treated with CO2 Laser and showing very good results.

Investigation of the Acute Effects of Dry Extract of Glycine Max on Postprandial Glycemia in Rats

The acute effects of Glycine max (GM) on post prandial glycemia (PPG) in male Wistar rats were investigated. All substances were orally administered by gavage in overnight fasted animals. The elevation of PPG promoted by starch (1g/kg) was prevented by GM (2.5 mg/kg, 5.0 mg/kg, 7.5 mg/kg, 10.0 mg/kg, and 100.0 mg/kg). In conclusion GM showed potential antidiabetic effect.

A comparison of the effects of oral glutamine dipeptide, glutamine, and alanine on blood amino acid availability in rats submitted to insulin-induced hypoglycemia.

We compared the effects of oral administration of high-dose or low-dose glutamine dipeptide (GDP), alanine (ALA), glutamine (GLN), and ALA + GLN on the blood availability of amino acids in rats submitted to insulin-induced hypoglycemia (IIH). Insulin detemir (1 U/kg) was intraperitoneally injected to produce IIH; this was followed by oral administration of GDP, GLN + ALA, GLN, or ALA. We observed higher blood levels of GLN, 30 min after oral administration of high-dose GDP (1000 mg/kg) than after administration of ALA (381 mg/kg) + GLN (619 mg/kg), GLN (619 mg/kg), or ALA (381 mg/kg). However, we did not observe the same differences after oral administration of low-dose GDP (100 mg/kg) compared with ALA (38.1 mg/kg) + GLN (61.9 mg/kg), GLN (61.9 mg/kg), or ALA (38.1 mg/kg). We also observed less liver catabolism of GDP compared to ALA and GLN. In conclusion, high-dose GDP promoted higher blood levels of GLN than oral ALA + GLN, GLN, or ALA. Moreover, the lower levels of liver catabolism of GDP, compared to ALA or GLN, contributed to the superior performance of high-dose GDP in terms of blood availability of GLN.

Tadalafil inhibits the cAMP stimulated glucose output in the rat liver.

The purpose of the present work was to verify if tadalafil affects hepatic glucose output, one of the primary targets of cAMP, in the isolated perfused rat liver. No effects on glycogen catabolism and oxygen uptake were found under basal conditions for tadalafil concentrations in the range between 0.25 and 10 µM. However, tadalafil had a clear and time-dependent inhibitory effect on the cAMP- and glucagon-stimulated glucose release. Constant infusion of tadalafil in the range between 0.25 and 10 µM eventually abolished 100% of the stimulatory action of those effectors. The tadalafil concentrations producing half-maximal rates of inhibition of the cAMP and glucagon stimulated glycogenolysis were 0.46±0.04 and 1.07±0.16 µM, respectively. These concentrations are close to the plasma peak concentrations in patients after ingestion of 20 mg tadalafil. The drug also diminished the activity of glycogen phosphorylase a and increased the activities of glucose 6-phosphatase, glucokinase, pyruvate kinase and glucose 6-phosphate dehydrogenase. These actions occurred only in the cellular environment. Tadalafil did not affect binding of cAMP to protein kinase A. Diminution of cAMP-stimulated glucose output is the opposite of what can be expected from a phosphodiesterase inhibition, the most common effect attributed to tadalafil. Diminution of glucose output by tadalafil can be attributed (a) to an interference with glycogen phosphorylase stimulation and (b) to an increased futile cycling of glucose 6-phosphate and glucose with a concomitant increased flow of hexose units into cellular metabolic pathways. The effects described in the present work may prove to represent important side effects of tadalafil.

Hypoglycemia induced by insulin as a triggering factor of cognitive deficit in diabetic children.

This paper provides an overview of insulin-induced hypoglycemia as a triggering factor of cognitive deficit in children with type 1 diabetes mellitus. For this purpose, databases from 1961 to 2013 were used with the objective of detecting the primary publications that address the impact of hypoglycemia on cognitive performance of diabetic children. The results obtained from experimental animals were excluded. The majority of studies demonstrated that the cognitive deficit in diabetic children involves multiple factors including duration, intensity, severity, and frequency of hypoglycemia episodes. Additionally, age at the onset of type 1 diabetes also influences the cognitive performance, considering that early inception of the disease is a predisposing factor for severe hypoglycemia. Furthermore, the results suggest that there is a strong correlation between brain damage caused by hypoglycemia and cognitive deterioration. Therefore, a more cautious follow-up and education are needed to impede and treat hypoglycemia in children with diabetes mellitus.

Adrenergic metabolic and hemodynamic effects of octopamine in the liver.

The fruit extracts of Citrus aurantium (bitter orange) are traditionally used as weight-loss products and as appetite suppressants. A component of these extracts is octopamine, which is an adrenergic agent. Weight-loss and adrenergic actions are always related to metabolic changes and this work was designed to investigate a possible action of octopamine on liver metabolism. The isolated perfused rat liver was used to measure catabolic and anabolic pathways and hemodynamics. Octopamine increased glycogenolysis, glycolysis, oxygen uptake, gluconeogenesis and the portal perfusion pressure. Octopamine also accelerated the oxidation of exogenous fatty acids (octanoate and oleate), as revealed by the increase in ¹4CO2 production derived from ¹4C labeled precursors. The changes in glycogenolysis, oxygen uptake and perfusion pressure were almost completely abolished by α1-adrenergic antagonists. The same changes were partly sensitive to the ß-adrenergic antagonist propranolol. It can be concluded that octopamine accelerates both catabolic and anabolic processes in the liver via adrenergic stimulation. Acceleration of oxygen uptake under substrate-free perfusion conditions also means acceleration of the oxidation of endogenous fatty acids, which are derived from lipolysis. All these effects are compatible with an overall stimulating effect of octopamine on metabolism, which is compatible with its reported weight-loss effects in experimental animals.

Oral glutamine is superior than oral glucose to promote glycemia recovery in mice submitted to insulin-induced hypoglycemia.

The effect of the oral administration of blood glucose precursors on glycemia recovery and liver glucose production in fasted mice subjected to insulin-induced hypoglycemia (IIH) was investigated. IIH was obtained with increasing doses (from 0.5 to 2.0 U·kg(-1)) of intraperitoneal regular insulin where glycemia was evaluated from 0 to 300 min after insulin injection. The dose of 1.0 U·kg(-1) showed the best results, that is, a clear glycemia recovery phase without convulsions or deaths. Thus, this dose was used in all experiments. Afterwards, mice submitted to IIH received orally by gavage: saline (control group), glucose (100 mg·kg(-1)), glycerol (100 mg·kg(-1)), lactate (100 mg·kg(-1)), alanine (100 mg·kg(-1)), or glutamine (100 mg·kg(-1)). It was observed that glutamine was more effective in promoting glycemia recovery if compared with glucose, lactate, glycerol, or alanine. In agreement with these results, the best performance in terms of liver glucose production was obtained when glutamine was used as glucose precursors. These results open perspectives for clinical studies to investigate the impact of oral administration of gluconeogenic amino acids to promote glycemia recovery during hypoglycemia.

The impact of multidrug therapy on the epidemiological pattern of leprosy in Juiz de Fora, Brazil u

Investigou-se o impacto da poliquimioterapia (PQT) no perfil epidemiológico da hanseníase em Juiz de Fora, Brasil, de 1978 a 1995. Fez-se uma avaliaçäo de 1.283 prontuários, de acordo com o esquema terapêutico adotado em dois diferentes períodos. Desde a introduçäo da PQT, em 1987, a prevalência da hanseníase caiu de 22 pacientes/dez mil habitantes para 5,2 pacientes/dez mil habitantes em 1995. A incidência da doença foi menor no período II (1987-1995) em comparaçäo ao período I (1978-1986). A diminuiçäo da prevalência e da incidência está mais relacionada à eficácia das drogas que a uma queda na identificaçäo da infecçäo, já que tanto a procura espontânea quanto os encaminhamentos aumentaram significativamente do período I para o período II. Em ambos os períodos, a forma clínica mais freqüente foi a multibacilar (ñ68 por cento), e o contato intradomiciliar foi o maior fator de risco conhecido associado à infecçäo. Um aumento de pacientes muito velhos ou muito novos foi observado no período II. Os resultados indicam que o esquema PQT tem sido eficaz no combate à hanseníase e tem aumentado a conscientizaçäo e o conhecimento da doença.