Search

The study of the biological activity of trypsin isoforms in aqueous-organic media is of great interest to various fields of knowledge and biochemistry applications. Thus enzymatic, structural, and energetic properties of bovine β- and α-trypsin isoforms were compared in aqueous-organic media using 30 mg of each isoform. The results showed that the changes induced on the structure and activity of the same trypsin isoform occur at different concentrations. Better results for activity (ionic strength of 0.11 mol·L -1 , at 37 °C and pH 8.0) were found in 0-40% of ethanolic media in which the activity for β-trypsin was about 60% higher than ɑ-trypsin. The ethanolic system does not cause significant changes in the level of secondary structure but the β-trypsin isoform undergoes a major rearrangement. The use of until 60% (v/v) ethanol showed that β-trypsin presents a denaturation process 17% more cooperative. The organic solvent causes redistribution in the supramolecular arrangement of both isoforms: all concentrations used induced the β-trypsin molecules to rearrange into agglomerates. The ɑ-trypsin rearranges into agglomerates up to 60% (v/v) of ethanol and aggregates at 80% (v/v) of ethanol. Both isoforms keep the enzymatic activity up to 60% (v/v) of ethanol., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The endocannabinoid system is capable of modulating multiple physiological brain functions including learning and memory. Moreover, there is evidence that the processes of acquisition and consolidation have distinct biological basis. We used the cannabinoid agonist WIN 55,212-2 (WIN-2) to investigate whether chronic CB1 activation affects acquisition and consolidation differently by evaluating gene expression in the hippocampus (HIP) and prefrontal cortex (PFC). Swiss mice were treated with WIN-2 (2 mg/kg) and submitted to the Morris water maze to evaluate different aspects of memory. We observed short-term memory impairment in acquisition of the spatial task while consolidation remained unchanged. In the PFC, animals that received WIN-2 prior to the task exhibited increased expression of the 2-AG synthesis enzyme diacylglycerol lipase and decreased levels of the degradation enzyme monoacylglycerol lipase, while mice that were treated after the task for the evaluation of consolidation exhibited the opposite profile. With respect to genes related to AEA metabolism, no correlation between the molecular and behavioral data could be established. In this sense, the cognitive impairment in the acquisition promoted by WIN-2 treatment may be related to a possible increase in the concentration of 2-AG in the PFC. Overall, this study confirms the relevance of the endocannabinoid system in the modulation of cognitive processes. A better understanding of the mechanisms underlying endocannabinoids roles in cognition could provide guidance for the development of treatments to reduce the cognitive deficits caused by drug abuse., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes. A sub-lethal dose of commercial chlorpyrifos (20 mg/kg, i.p.) elicited signs of acute toxicosis during the first hours after its injection in rats. Twenty-four hours after treatment, this single dose of chlorpyrifos induced a depressive-like behaviour in the rat forced swimming test without impairing locomotor activity. At this time (24 h), chlorpyrifos decreased plasma butyrylcholinesterase (BChE) activity and hippocampal, striatal and prefrontal cortical AChE activity in rats. The behavioural and biochemical consequences of acute chlorpyrifos poisoning do not seem to be long lasting, since 30 days later they were absent. We evaluated whether these behavioural and biochemical consequences of acute chlorpyrifos treatment would be reversed by the antidotes atropine (10 mg/kg i.p.) and/or pralidoxime (40 mg/kg; i.p.) given 1 h after poisoning. Pralidoxime partially reactivated the AChE activity in the prefrontal cortex, but not in the hippocampus and striatum. Atropine attenuated the depressive-like behaviour induced by chlorpyrifos in rats. Our results suggest that acute chlorpyrifos poisoning induces a transient depressive-like behaviour possible related to hippocampal AChE inhibition. They suggest that treatment with atropine and pralidoxime seems to be insufficient to counteract all the effects of OP acute poisoning, at least in rats., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The α-trypsin isoform is a globular protein that belongs to serine-protease family and has a polypeptide chain of 223 amino acid residues, six disulfide bridges and two domains with similar structures. The effects of aqueous-organic solvent (ethanol) in different concentration on the α-trypsin structure have been investigated by spectroscopic techniques and thermodynamic data analysis. The results from spectroscopic measurements, including far-UV Circular Dichroism, UV-vis absorption spectroscopy, intrinsic tryptophan fluorescence and dynamic light scattering (DLS) suggest the formation of partially folded states, instead of aggregate states, at high ethanol concentration (>60% v/v ethanol), with little loss of secondary structure, but with significant tertiary structure changes. The thermodynamic data (T m and ΔH) suggest a loosening of intramolecular weak interactions, which reflects in a flexibility increase such that the catalytic capacity can be increased or decreased according to the ethanol concentration into the system. Overall results we suggest that in range of 0-60% v/v ethanol/buffer, α-trypsin undergoes reversible multimerization phenomena with catalytic activity. However from 60% v/v ethanol/buffer, population of folded partially states with less catalytic activity are predominant., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Crack-cocaine addiction has increasingly become a public health problem worldwide, especially in developing countries. However, no studies have focused on neurobiological mechanisms underlying the severe addiction produced by this drug, which seems to differ from powder cocaine in many aspects. This study investigated behavioural, biochemical and molecular changes in mice inhaling crack-cocaine, focusing on dopaminergic and endocannabinoid systems in the prefrontal cortex. Mice were submitted to two inhalation sessions of crack-cocaine a day (crack-cocaine group) during 11 days, meanwhile the control group had no access to the drug. We found that the crack-cocaine group exhibited hyperlocomotion and a peculiar jumping behaviour ("escape jumping"). Blood collected right after the last inhalation session revealed that the anhydroecgonine methyl ester (AEME), a specific metabolite of cocaine pyrolysis, was much more concentrated than cocaine itself in the crack-cocaine group. Most genes related to the endocannabinoid system, CB1 receptor and cannabinoid degradation enzymes were downregulated after 11-day crack-cocaine exposition. These changes may have decreased dopamine and its metabolites levels, which in turn may be related with the extreme upregulation of dopamine receptors and tyrosine hydroxylase observed in the prefrontal cortex of these animals. Our data suggest that after 11 days of crack-cocaine exposure, neuroadaptive changes towards downregulation of reinforcing mechanisms may have taken place as a result of neurochemical changes observed on dopaminergic and endocannabinoid systems. Successive changes like these have never been described in cocaine hydrochloride models before, probably because AEME is only produced by cocaine pyrolysis and this metabolite may underlie the more aggressive pattern of addiction induced by crack-cocaine., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Research has identified a strong link between stress and drug use behaviours. Also, it has been established that the prolonged use of crack cocaine stimulates emotional, cognitive, neurological and social changes. This paper explores the psychological stressors that occur from crack cocaine use and the coping mechanisms used to mitigate them. This will provide an understanding of the intricate relationship between substance use and psychological well-being. Methodology: The study is qualitative and uses a descriptive phenomenological approach. The coping circumplex model is the theoretical model that underpins the study. Data was collected through 26 face-to-face in-depth semi-structured interviews with people who use crack cocaine. Data were analysed using thematic analysis. Participants consisted of 15 males and 11 females between the ages of 24–57 years, guaranteeing multiplicity within the study sample. Results: Cravings, financial burdens, relationship breakdown and emotional /cognitive stimulation were revealed as psychological stressors. Maladaptive coping which includes self-harm, isolation, not speaking about/not dealing with emotions and using substances were adopted by study participants. Also, positive coping such as seeking help and keeping busy were adopted by study participants. Social and environmental factors such as stigma, easy accessibility of crack and flashbacks served as barriers to positive coping. Positive coping was linked to the availability and easy accessibility to social support and strong family bonds, underlining the importance of accessible support systems in managing the challenges linked with crack cocaine use. Conclusion: The challenges faced by study participants in coping with the psychological stressors linked to their crack cocaine use highlight the importance of adopting personalised and comprehensive strategies to tackle the intricate dynamics between psychological stress, coping and crack cocaine use. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of a new non-invasive body contouring device in patients with localized fat in abdomen or in abdomen and hips. Additionally, we also evaluated the patient satisfaction with the procedure. Methods: Prospective and non-randomized open label study. The patients underwent four sessions, separated by 1 week each, with the Alma PrimeX, a non-invasive body contouring device that combines pulsed non-focus ultrasound and a Unipolar radiofrequency. The primary end point was the mean change in fat tissue thickness, assessed by diagnostic ultrasound, from baseline to 3-months after the last treatment-session. Results: Fifteen subjects were evaluated. As compared to pre-treatment thickness, Hodges-Lehmann median difference (95% CI) was − 85.3 (− 107.5 to − 62.0) mm, p = 0.0001; − 70.3 (− 95.0 to − 48.5) mm, p = 0.0001; − 100.0 (− 140.5 to − 49.5) mm, p = 0.0039; and − 71.8 (− 132.5 to − 23.0) mm, p = 0.0078 in infraumbilical, supraumbilical, right hip, and left hip, respectively. Pretreatment fat volume was significantly reduced from 32.9% to 31.2%, p = 0.0006. The median (interquartile range) degree of patient satisfaction was 4.0 (1.0–5.0), with 13 (86.7%) patients being "Highly satisfied" or "Satisfied" with the treatment results. The most common adverse event was discomfort, followed by erythema. All the adverse events were mild and were successfully resolved without treatment. Conclusions: Combine therapy of a Pulsed non-focus ultrasound and Unipolar radiofrequency using the non-invasive device Alma PrimeX was an effective and safe treatment for reducing fat tissue thickness in abdomen and hips in patients with localized fat. Patients' satisfaction with the procedure was high. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and complex neurodegenerative disease, distinguished by the presence of lesions in the central nervous system (CNS) due to exacerbated immunological responses that inflict oligodendrocytes and the myelin sheath of axons. In recent years, studies have focused on targeted therapeutics for MS that emphasize the role of G protein-coupled receptors (GPCRs), specifically cannabinoids receptors. Clinical studies have suggested the therapeutic potential of cannabinoids derived from Cannabis sativa in relieving pain, tremors and spasticity. Cannabinoids also appear to prevent exaggerated immune responses in CNS due to compromised blood–brain barrier. Both, endocannabinoid system (ECS) modulators and cannabinoid ligands actively promote oligodendrocyte survival by regulating signaling, migration and myelination of nerve cells. The cannabinoid receptors 1 (CB1) and 2 (CB2) of ECS are the main ones in focus for therapeutic intervention of MS. Various CB1/CB2 receptors agonists have been experimentally studied which showed anti-inflammatory properties and are considered to be effective as potential therapeutics for MS. In this review, we focused on the exacerbated immune attack on nerve cells and the role of the cannabinoids and its interaction with the ECS in CNS during MS pathology. [ABSTRACT FROM AUTHOR]

Adrenal tumors are common tumors in urology and they can be further divided into functioning and nonfunctioning tumors according to whether there is uncommon endocrine function. In clinical practice, the early identification and accurate assessment of adrenal tumors are essential for the guidance of subsequent treatment. However, a nonfunctioning adrenal tumor often lacks obvious clinical symptoms, making it difficult to be timely and precisely diagnosed by conventional examinations. Therefore, a rapid and accurate method for identifying the functioning and nonfunctioning adrenal tumors is urgently required to achieve precise treatment of adrenal tumors. In this study, surface-enhanced Raman spectroscopy was investigated as a diagnostic tool to identify the blood serum samples from healthy volunteers as well as the patients with functioning and nonfunctioning adrenal tumors. Based on the SERS peak analysis, abnormal glycolysis, DNA/RNA, and amino acid metabolites were found to be potential biomarkers for identifying patients with adrenal tumors, while metabolites related to disordered protein catabolism and excessive hormone secretion were expected to further differentiate functioning adrenal tumors from nonfunctioning adrenal tumors. In addition, principal component analysis followed by support vector machine (PCA-SVM) was further applied on those serum SERS measurements, and the classification accuracies of 96.8% and 84.5% were achieved for differentiating healthy group versus adrenal tumor group and functioning adrenal tumor group versus nonfunctioning adrenal tumor group, respectively. The results have demonstrated the prodigious potential of precise adrenal tumor diagnosis by using the blood serum surface-enhanced Raman spectroscopy technique. [ABSTRACT FROM AUTHOR]

Background: Crack-cocaine dependence is a serious public health issue, related to several psychiatric and psychosocial problems. Crack-cocaine users are usually embedded in a context of great social vulnerability, often associated with violence, poverty, family conflict and easy and early access to alcohol, tobacco and other drugs.Methods: This cross-sectional study enrolled a consecutive sample of 577 patients admitted to 20 therapeutic communities located in Southern Brazil, between September 2012 and September 2013. A structured interview assessed life-time exposure to risk and protective factors for drug use, such as parental monitoring in childhood, deviant behaviors and peer pressure.Results: Presence of family conflict (p = 0.002), maltreatment (p = 0.016), and deviant behavior prior to age 15 in a bivariate analysis predicted an earlier age of crack-cocaine initiation, whereas adolescents experiencing parental monitoring during adolescence started use later (p < 0.001). In the multivariate model, perceptions related to ease of access of illicit drugs (marijuana: p = 0.028, 95% CI = - 3.81, - 0.22; crack-cocaine: p < 0.001, 95% CI = - 7.40, - 4.90), and deviant behavior (threatening someone with a gun: p = 0.028, 95% CI = - 2.57, - 0.14) remained independent predictors of early age of crack-cocaine initiation.Conclusions: Early onset of crack-cocaine use seems to be associated with exposure to family conflict, easy access to drugs and deviant behavior. Treatment and preventive programs should take these factors into account when designing and implementing community interventions. [ABSTRACT FROM AUTHOR]

Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine. [ABSTRACT FROM AUTHOR]

Obesity increases sympathetic nerve activity (SNA) in men, but not women. Here, we review current evidence suggesting that sexually dimorphic sympathoexcitatory responses to leptin and insulin may contribute. More specifically, while insulin increases SNA similarly in lean males and females, this response is markedly amplified in obese males, but is abolished in obese females. In lean female rats, leptin increases a subset of sympathetic nerves only during the high estrogen proestrus reproductive phase; thus, in obese females, because reproductive cycling can become impaired, the sporadic nature of leptin-induced sympathoexcitaton could minimize its action, despite elevated leptin levels. In contrast, in males, obesity preserves or enhances the central sympathoexcitatory response to leptin, and current evidence favors leptin's contribution to the well-established increases in SNA induced by obesity in men. Leptin and insulin increase SNA via receptor binding in the hypothalamic arcuate nucleus and a neuropathway that includes arcuate neuropeptide Y (NPY) and proopiomelanocortin (POMC) projections to the paraventricular nucleus. These metabolic hormones normally suppress sympathoinhibitory NPY neurons and activate sympathoexcitatory POMC neurons. However, obesity appears to alter the ongoing activity and responsiveness of arcuate NPY and POMC neurons in a sexually dimorphic way, such that SNA increases in males but not females. We propose hypotheses to explain these sex differences and suggest areas of future research. [ABSTRACT FROM AUTHOR]

Background and objectives: Nowadays, there are several noninvasive technologies being used for improving of body contouring. The objectives of this pilot study were to verify the effectiveness of the Heccus® device, emphasizing the synergism between nonfocused ultrasound plus Aussie current in the improvement of body contour, and to determine if the association of this therapy with whole-body vibration exercises can have additional positive effects in the results of the treatments. Subjects and methods: Twenty healthy women aged 20-40 years participated in the study. Ten patients received Combined Therapy treatment (G1) and the other 10 participants received Combined Therapy with additional vibratory platform treatment (G2). Anthropometric and standardized photography analysis, ultrasonography, cutometry and self-adminestered questionnaires of tolerance and satisfaction levels with the treatment were used. Results: Compared with baseline values, reduction of fat thickness was observed by ultrasonography in the posterior thigh area in the G1 group (P<0.05) and in the buttocks (P<0.05) and the posterior thigh areas (P<0.05) in the G2. All the treated areas in both groups showed reduction in cellulite degree in the buttocks, G1 (P<0.05) and G2 (P<0.05), and in posterior thigh areas, G1 (P<0.05) and G2 (P<0.05). Optimal improvement of skin firmness (G1, P<0.0001; G2, P=0.0034) in the treated areas was observed in both groups. Conclusion: We conclude that the synergistic effects of the Combined Therapy (nonfocused ultrasound plus Aussie current) might be a good option with noninvasive body contouring treatment for improving the aspect of the cellulite, skin firmness and localized fat. If used in association with the whole-body vibratory platform, the results can be better, especially in the treatment of localized fat. Further studies with larger sample size should be performed to confirm these results. [ABSTRACT FROM AUTHOR]

The neurotoxin MPTP has long been used to create a mouse model of Parkinson’s disease (PD). Indeed, several MPTP analogues have been developed, including 2′-CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more potently than MPTP. However, no study on behavioral and molecular alterations in response to 2′-CH3-MPTP has been carried out so far. In the present work, 2′-CH3-MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5 days) and histological, biochemical, molecular and behavioral alterations were evaluated. We show that, despite a dose-dependent-like pattern observed for nigrostriatal dopaminergic neuronal death and dopamine depletion, dose-specific alterations in dopamine metabolism and in the expression of dopaminergic neurotransmission-associated genes could be related to specific motor deficits elicited by the different doses tested. Interestingly, 2′-CH3-MPTP leads to increased DAT and MAO-B transcription, which could explain, respectively, its higher potency and the requirement of higher doses of MAO inhibitors to prevent nigrostriatal neuronal death when compared to MPTP. Also, perturbations in dopamine metabolism as well as possible alterations in dopamine bioavailability in the synaptic cleft were also identified and correlated with strength and ambulation deficits in response to specific doses. Overall, the present work brings new evidence supporting the distinct effects of 2′-CH3-MPTP when compared to its analogue MPTP. Moreover, our data highlight the utmost importance of a precise experimental design, as different administration regimens and doses yield different biochemical, molecular and behavioral alterations, which can be explored to study specific aspects of PD. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1-7)/MAS, whose end point is the metabolite ANG- (1-7). ACE2 and other enzymes can form ANG-(1-7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1-7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1-7) in physiology and disease, with particular emphasis on the brain. [ABSTRACT FROM AUTHOR]

Brazil is a global agricultural commodity producer and the largest consumer of pesticides. Pesticide use in Brazil comprised 549 280 tons in 2018. In the country, soybean, corn, and sugar cane are extensively produced, which are the most pesticides demanding crops. In the last years, the records of new pesticides were the highest in the historical series. They can persist in soil or water, accumulate in organisms, and contaminate workers and the general population through the air, water, or food. This review aimed to gather toxicological data obtained by animal models exposed to 4 pesticides: glyphosate, chlorpyrifos, abamectin, and 2,4-D. An additional goal was to compose an overview of how this subject has been approached, surveying which research groups are working on this field, where they are located, and relations with pesticides used in those regions. We collected the papers from the platforms PubMed, Scopus, Scielo, and Web of Science, performed in Brazil from 2014 to 2019. After two-step blind selection using the software Rayyan QCRI by different authors, 67 studies were selected to extract data. We observed that research is more concentrated in the South region, followed by the Southeast and Midwest, with 43%, 32%, and 23% of the studies, respectively. The prevalent institutions are from the states of Rio Grande do Sul, São Paulo, and Goiás. The effects on a variety of biomarkers help predict the potential risks to humans and nontarget organisms. The prevalent animal model was fish (36%). Overall, the main toxic effects evaluated were mortality, abnormalities in the blood cells, developmental abnormalities, and behavior alterations. Integr Environ Assess Manag 2021;17:507-520. © 2020 SETAC., (© 2020 SETAC.)

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, being characterized by dopaminergic neurodegeneration of substantia nigra pars compacta. PD pharmacotherapy has been based on dopamine replacement in the striatum with the dopaminergic precursor 3,4-dihydroxyphenylalanine ( l-DOPA) and/or with dopaminergic agonists, alongside anticholinergic drugs in order to mitigate the motor abnormalities. However, these practices neither prevent nor stop the progression of the disease. Environmental enrichment (EE) has effectively prevented several neurodegenerative processes, mainly in preclinical trials. Several studies have demonstrated that EE induces biological changes, bearing on cognitive enhancement, neuroprotection, and on the attenuation of the effects of stress, anxiety, and depression. Herein, we investigated whether EE could prevent the motor, biochemical, and molecular abnormalities in a murine model of PD induced by 1-methyl-4-phenyl-2,3-dihydropyridine (MPTP). Our results show that EE does not prevent the dopaminergic striatal depletion induced by MPTP, despite having averted the MPTP-induced hyperlocomotion. However, it was able to slow down and avoid, respectively, the 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion. Analysis of dopaminergic mRNA alterations in the midbrain showed that D1R expression was increased by MPTP, while the normal expression level of this receptor was restored by EE. As for the cholinergic system, MPTP led to a decrease in the ChAT gene expression while increasing the expression of both AChE and M1R. EE attenuated and prevented-respectively-ChAT and M1R gene expression alterations triggered by MPTP in the midbrain. Overall, our data brings new evidence supporting the neuroprotective potential of EE in PD, focusing on the interaction between dopaminergic and cholinergic systems. [ABSTRACT FROM AUTHOR]

Several soil-derived Actinobacteria produce secondary metabolites that are proven specific and potent inhibitors of the human angiotensin-I-converting enzyme (ACE), a key target for the modulation of hypertension through its role in the renin-angiotensin-aldosterone system. K-26-DCP is a zinc dipeptidyl carboxypeptidase (DCP) produced by Astrosporangium hypotensionis, and an ancestral homologue of ACE. Here we report the high-resolution crystal structures of K-26-DCP and of its complex with the natural microbial tripeptide product K-26. The experimental results provide the structural basis for better understanding the specificity of K-26 for human ACE over bacterial DCPs. Database Structural data are available in the PDB under the accession numbers and . [ABSTRACT FROM AUTHOR]

It has been postulated that the protective effects of lower body subcutaneous adipose tissue (LBSAT) occur via its ability to sequester surplus lipid and thus serve as a “metabolic sink.” However, the mechanisms that mediate this protective function are unknown thus this study addresses this postulate. Ad libitum, chow-fed mice underwent Sham-surgery or LBSAT removal (IngX, inguinal depot removal) and were subsequently provided chow (Chow; typical adipocyte expansion) or high fat diet (HFD; enhanced adipocyte expansion) for 5 weeks. Primary outcome measures included glucose tolerance and subsequent insulin response, muscle insulin sensitivity, liver and muscle triglycerides, adipose tissue gene expression, and circulating lipids and adipokines. In a follow up study the consequences of extended experiment length post-surgery (13 wks) or pre-existing glucose intolerance were examined. At 5 wks post-surgery IngX in HFD-fed mice reduced glucose tolerance and muscle insulin sensitivity and increased circulating insulin compared with HFD Sham. In Chow-fed mice, muscle insulin sensitivity was the only measurement reduced following IngX. At 13 wks circulating insulin concentration of HFD IngX mice continued to be higher than HFD Sham. Surgery did not induce changes in mice with pre-existing glucose intolerance. IngX also increased muscle, but not liver, triglyceride concentration in Chow- and HFD-fed mice 5 wks post-surgery, but chow group only at 13 wks. These data suggest that the presence of LBSAT protects against triglyceride accumulation in the muscle and HFD-induced glucose intolerance and muscle insulin resistance. These data suggest that lower body subcutaneous adipose tissue can function as a “metabolic sink.” [ABSTRACT FROM AUTHOR]