Progressive Decrease In Body Weight Research Articles

Evaluation of antidiabetic potential of Hibiscus rosa sinensis on streptozotocin-induced diabetes on Wistar albino rats

The chronic metabolic disease known as diabetes mellitus causes hyperglycemia in the body. Antioxidant and antidiabetic qualities are well-known benefits of Hibiscus rosa sinensis (HRS). In this work, diabetic Wistar albino rats were used to assess the antidiabetic properties of HRS flower extract. A total of 18 animals were taken and divided into three groups (n = 6) – (Group 1): Normal control group, (Group 2): Diabetic control group, (Group 3): Diabetic group treated with a 125 mg/kg dose of HRS flower extract. Group 2 animals showed a progressive decrease in body weight, while Group 1 animals showed a considerable gain in body weight. After overcoming the weight loss, Group 3 animals also showed an increase in body weight that was similar to Group 1. Group 2 animals had blood glucose levels higher than 400 mg/dL, but Group 1 animals had blood glucose levels below 200 mg/dL throughout the experiment. Group 3 animals first had glucose levels higher than 350 mg/dL and then lower than 200 mg/dL, comparable to Group 1 animals. Upon histological examination, the pancreatic islets of Group 2 animals showed vacuolation, necrosis, and degeneration. The animals in Group 3 displayed regenerated islets of Langerhans and enhanced pancreatic anatomy. The animals in Group 3 also returned to normal in terms of body weight and blood glucose levels, similar to those in Group 1. These findings show that Hibiscus rosa sinensis has potential as an alternative diabetic treatment; further research is needed to fully understand its modes of action and long-term effects.

Principles of management of patients with short bowel syndrome

Short bowel syndrome (SBS) is a rare disease accompanied by the phenomena of malabsorption (impaired absorption of food) and maldigestion (phenomena of creato-, steato-and amilorrhea), as a result of resection of most of the small intestine (usually with a residual part of the intestine less than 200 cm) from – due to various etiological factors. One of the severe complications of this syndrome is the development of intestinal failure, which can be manifested by the occurrence of water, electrolyte and white matter disturbances, hypovitaminosis, and deficiency of micro-and macronutrients. It is possible to suspect the development of intestinal failure if the patient continues to have repeated diarrhea 2–3 months after surgery and a progressive decrease in body weight by 5% or more of the initial weight within a month. Therefore, an important aspect in the treatment of SBS is the correction of electrolyte disturbances and maintenance of nutritional status. However, the severity of the patient’s condition is often determined not only by the course of the disease itself, but also by the long-term use of parenteral nutrition after surgery. Therefore, an important aspect in the management of patients with SBS is the cessation of parenteral nutrition as early as possible and the transition to a physiological nature of food intake. This can be achieved both by choosing certain surgical treatment techniques and by using drug therapy – an analogue of glucagon-like peptide-2 – Teduglutide, which increases the functional ability of enterocytes to absorb. SBS is a significant social problem due to the high mortality rate in childhood and a significant percentage of disability in people of working age, which makes it highly relevant to discuss the management strategy for this category of patients.

RNAi knockdown of microtubule‐associated protein Tau prevents axonal damage and clears pre‐existing Tau aggregates in P301S transgenic tauopathy model mice

AbstractBackgroundThe hyperphosphorylation and subsequent aggregation of the microtubule‐associated protein Tau (encoded by the MAPT gene) is one of the major histopathological hallmarks of numerous tauopathies, including Alzheimer’s disease and progressive supranuclear palsy. The intracellular accumulation of aggregated Tau is associated with neuronal loss and disease progression in tauopathies. There is a high‐unmet need to identify strategies to target the intracellular accumulation of Tau aggregates with the aim of slowing tauopathy progression.MethodTo model this, we used mice carrying multiple copies of a transgene with a prion promoter driving human MAPT with human tauopathy‐inducing mutation P301S. P301S‐Tau transgenic mice progressively accumulate neuroglial Tau aggregates associated with axonal damage, gliosis, body weight loss, and ambulatory dysfunction.ResultP301S mice treated with a single intracerebroventricular injection of Tau siRNA at eight months of age, had a sustainable decrease in MAPT mRNA and soluble Tau protein for three months following siRNA treatment (reduced ∼83% and ∼59%, respectively). siRNA treatment also prevented the progressive decrease in body weight and abrogated axonal damage, evidenced by decreased neurofilament light (NFL) chain in plasma and cerebrospinal fluid of eleven‐month‐old mice. Importantly, immunohistochemical analysis of misfolded Tau in vivo and HEK293‐4RD‐CFP/YFP Tau aggregate biosensor assay testing in vitro revealed a ∼97% decrease of Tau aggregates in the eleven‐month‐old mice, suggesting there exists a yet‐to‐be identified mechanism of Tau fibril clearance.ConclusionTogether, these results suggest an RNAi therapeutics approach targeting of MAPT mRNA may be sufficient to improve multiple parameters of tauopathy disease progression and a provide a compelling rationale for further development of Tau‐lowering strategies.

Exploring the potential targets of Biling Weitong Granules on visceral hypersensitivity through integration of network pharmacology and in vivo analysis

Ethnopharmacological relevanceBiling Weitong Granules (BLWTG) are a newly developed traditional Chinese medicine prescription based on the ancient prescription Jinlingzi San and Zuojin Wan. It is used for the treatment of functional gastrointestinal disorders (FGIDs) featured as visceral hypersensitivity (VH). However, its active ingredients and protein targets involved still remain unknown. Aim of the studyTo explore the potential targets of BLWTG for the treatment of visceral hypersensitivity. Materials and methodsActive components and their protein targets of BLWTG were screened from TCMSP database and the component-target network were constructed with Cytoscape software. Irritable bowel syndrome (IBS) was the representative disease in this study and information on its linked pathways was obtained from NCBI, Drugbank and Genecard. Target pathways of BLWTG were analyzed through KEGG to verify the correlation with IBS related pathways.Then, the VH mouse models was induced by maternal separation (MS), randomly divided into normal saline (NS),BLWTG1 (low-dosage) and BLWTG2 (high-dosage) group. After intervention, threshold intensity of colorectal distension (CRD) and body weight were measured to evaluate relief of IBS symptoms. Elisa was performed to evaluate 5-HT concentration changes of colon tissues. Flow cytometry was performed to assess changes of colon eosinophils and mast cells proportion. Transcriptome sequencing was employed to analyze changes of pathways and differential genes. Results199 protein targets and 132 active components of BLWTG were identified. KEGG analysis revealed the overlap between BLWTG target pathways and IBS related pathways such as neuroactive ligand-receptor interaction, tryptophan metabolism and inflammatory reaction. 34 genes were not only BLWTG target proteins but also recognized targets for treating IBS.After maternal separation (MS), the mice showed a significant decrease in threshold intensity of CRD, a progressive decrease in body weight and an increase of 5-HT concentration of colon tissue. The proportion of mast cells and eosinophils in the colon increased. Differential genes including Hp,Ido1 and Aqp7 were significantly increased in MS mice group and IBS-related pathways were upregulated. After treatment of BLWTG, threshold intensity of CRD and body weight were significantly improved and IBS related pathways were downregulated. In addition, among BLWTG protein targets, Il1b,Tnf,Adrb1 and Nos2 were found upregulated in MS+NS mice and downregulated after BLWTG intervention through combination of transcriptome sequencing. ConclusionsIn maternal separation-induced mouse models, BLWTG could alleviate visceral hypersensitivity, possibly through downregulation of 5-HT concentration and eosinophils and mast cells proportion in colon and critical pathways such as neuroactive ligand-receptor pathway. Potential targets of BLWTG including Il1b,Tnf,Adrb1 and Nos2 were found through integration of network pharmacology database and transcriptome sequencing, providing evidence for further study on mechanisms underlying visceral hypersensitivity.

Metabolic effects of the liraglutide: a discussion of the results of clinical observations

Objective: to discuss the features of the use of the drug liraglutide for the treatment of patients with obesity, to analyze the metabolic parameters dynamic and the difficulties that arise during therapy, based on our own clinical observations.Materials and methods: the article provides an analysis of our own clinical observations of patients aged 54 and 47 years who received liraglutide therapy for exgenous constitutional obesity of the II degree. According to the examination results, both patients showed hyperinsulinemia and insulin resistance signs, lipid metabolism disorders. There were no episodes of acute pancreatitis in the past. Heredity for medullary thyroid cancer is not burdened, thyroid status is normal. Dose liraglutide escalation is recommended on a schedule 0.6 mg per week.Results: during therapy with liraglutide, patients under observation experienced a gradual progressive decrease in body weight against the background of a decrease in appetite and a decrease in the amount of food consumed. In the dynamics, there was a tendency to normalize the initial metabolic disorders: a decrease in insulin resistance and hyperinsulinemia, carbohydrate metabolismdisorders and lipid profile.Conclusion: the results of our own clinical observations indicate the effectiveness of the drug liraglutide use in the treatment of patients with obesity, not only to achieve the target weight loss indicators, but also to correct the initial disorders of the metabolic status.

Neutralization of GDF15 Prevents Anorexia and Weight Loss in the Monocrotaline-Induced Cardiac Cachexia Rat Model.

Growth and differentiation factor 15 (GDF15) is a cytokine reported to cause anorexia and weight loss in animal models. Neutralization of GDF15 was efficacious in mitigating cachexia and improving survival in cachectic tumor models. Interestingly, elevated circulating GDF15 was reported in patients with pulmonary arterial hypertension and heart failure, but it is unclear whether GDF15 contributes to cachexia in these disease conditions. In this study, rats treated with monocrotaline (MCT) manifested a progressive decrease in body weight, food intake, and lean and fat mass concomitant with elevated circulating GDF15, as well as development of right-ventricular dysfunction. Cotreatment of GDF15 antibody mAb2 with MCT prevented MCT-induced anorexia and weight loss, as well as preserved lean and fat mass. These results indicate that elevated GDF15 by MCT is causal to anorexia and weight loss. GDF15 mAb2 is efficacious in mitigating MCT-induced cachexia in vivo. Furthermore, the results suggest GDF15 inhibition is a potential therapeutic approach to alleviate cardiac cachexia in patients.

An Experimental Model of Direct Acute Lung Injury in Rats Caused by Intratracheal Administration of Lipopolysaccharide from Salmonella enterica

An experimental model of direct acute lung injury was developed by intratracheal administration of lipopolysaccharide from Salmonella enterica (LD50 = 20 mg/kg). The dynamics of animal lethality, body weight, temperature and the severity of pathomorphological changes in the lung tissue were analyzed. It was found that the developed model is accompanied by a progressive decrease in body weight by 15%, persistent hypothermic reaction, pronounced edema and inflammatory reaction in the lung tissue within 4 days following lipopolysaccharide administration. The simplicity and reproducibility of the developed experimental model make it useful for preclinical research aimed at selection of candidate drugs for the prevention and treatment of acute respiratory distress syndrome.

CXCR4 ANTAGONIST AMD3100 PROMOTES MILD IMPROVEMENTS OF CARDIAC FUNCTION AND PULMONARY MECHANICS IN PULMONARY HYPERTENSIVE RATS

Background Pulmonary arterial hypertension (PAH) is a lethal cardiopulmonary disease characterized by an increase in resting pulmonary pressure ≥25 mmHg. Poor survival and functional limitations of PAH patients have fueled research for new alternative therapeutic strategies. So far, pre-clinical findings suggested promising effects of stem cell-based therapies. AMD3100 is a highly selective CXCR4 antagonist that enhances autologous bone marrow-derived stem cell mobilization and is currently used in stem cell transplantation and the treatment of leukemia. So far, however, it remains unclear whether AMD3100 can provide salutary effects in the treatment of PAH. Methods PAH was induced in adult male Wistar rats (Protocol number 087/15) by an intraperitoneal injection of monocrotaline (MCT, 60 mg/kg IP), while the Control (CTL) group was treated an equivalent volume of vehicle. Two weeks after the MCT injection, MCT-administered rats were randomly treated with AMD3100 (1 mg/kg/day IP for 14 days) or vehicle, totalling 3 groups: CTL, MCT, and AMD3100. Echocardiography and pneumotachography were used to assess cardiac function and pulmonary mechanics, respectively. Right ventricular (RV) hypertrophy was assessed by the Fulton index. Data were analyzed with One-way and Two-way ANOVA (Prism®, GraphPad) and were expressed as mean ± SEM. Results MCT and AMD3100 groups exhibited an equally progressive decrease in body weight compared to the CTL group (p Conclusion Our study indicates that treatment with AMD3100 provides mild improvement of cardiac and pulmonary function in pulmonary hypertensive rats.

Congenital short bowel syndrome: a case report and review of the literature

Congenital short bowel syndrome is a rare condition of the newborn, with several reports demonstrating high mortality. For the first time in Russia, we report a case of treatment of a newborn girl with genetically confirmed congenital short bowel syndrome, and also provide a review of the literature on this syndrome. After birth, the child experienced constant vomiting of bile with a progressive decrease in body weight. The laparotomy for congenital adhesions between the loops of the small intestine with severe violations of the evacuation function revealed that the small bowel was 50 cm in length, confirming the diagnosis of congenital short bowel syndrome. The genetic test, using whole exome sequencing, identified a homozygous mutation in the CLMP gene in this patient. A positive result in the postoperative period was achieved using the protocol for the management of patients with short bowel syndrome. Currently, the girl is 11 months old, body weight is 9 kg, development is harmonious. Long-term survival of children with congenital short bowel syndrome is now possible if enteral feeds are introduced early to promote intestinal adaptation, with subsequent weaning off parenteral nutrition.

Mitochondrial Fusion Is Essential For Regulation Of Adult Skeletal Muscle Mass And Protein Synthesis

PURPOSE: Mitochondrial dynamics and the function and health of skeletal muscle are inextricably linked. To preserve proper function, muscle mitochondria undergo constant remodeling through fission and fusion events. Mitochondrial fission is regulated by fission 1 (Fis1) and dynamin-related protein 1 (Drp1), while fusion is regulated by three GTPases; mitofusin 1 and 2 (Mfn1, Mfn2) and optic atrophy 1 (Opa1). However, the role of mitochondrial fusion in adult skeletal muscle mass regulation is not fully understood. We hypothesized that genetic disruption of mitochondrial fusion in adult skeletal muscle will impair muscle function and growth. METHODS: We therefore developed and characterized adult inducible skeletal muscle specific Mfn1/2 double knockout mice (MFNDKO). Genetic deletion was induced in adult mice and confirmed by qPCR and western blot. Body/muscle size and composition was analyzed gravimetrically and by QMR. Muscle function was assessed by grip test. Interrogation of pathways regulating muscle mass, including atrophy and autophagy were performed by qPCR and western blotting. In vivo and in vitro protein synthesis rates were evaluated using a puromycin incorporation assay. RESULTS: MFNDKO mice exhibited a progressive decrease in body weight (~20% lower than CON, respectively; p < 0.05). This reduction in body weight was associated with a decrease in lean mass, confirmed by QMR, gastrocnemius wet weight and cross sectional area (50% and 36% reduction, respectively; p < 0.05). Gene profiling of pathways that regulate muscle homeostasis revealed upregulation of FBXO30, FBXO32, MT1 and CTSL (p < 0.05, all) suggesting an activation of muscle atrophy. Furthermore, muscles from MFNDKO mice revealed increased markers of autophagy with increased p62 mRNA and increased LC3II/I and p62 protein levels. Protein synthesis rates were decreased in vitro and in vivo (14% and 75%; p < 0.05, respectively) in MFNDKO muscle. CONCLUSIONS: Taken together, these observations suggest that normal mitochondrial fusion is required for maintaining normal adult skeletal muscle mass.

Russian sturgeon cultured in a subtropical climate shows weaken innate defences and a chronic stress response

Russian sturgeon (Acipenser gueldenstaedtii) has been successfully farmed in Uruguay for the past ten years. However, during the Uruguayan summer fish endure high water temperatures and increased bacterial infections that threaten aquaculture. Our understanding of sturgeon's immune system and its interplay with environmental factors like temperature is almost unknown. This study analysed the way in which seasonal variations affect enzymatic blood components of Russian sturgeon's innate defences, including the serum alternative complement pathway (ACP), ceruloplasmin (Cp) and lysozyme activities. Results showed that summertime conditions in the farm altered these defences in different ways, inducing a significant decrease in ACP and Cp, and an increase in lysozyme. In addition, serum levels of total protein and cortisol decreased in summer, suggesting a chronic stress response was induced in parallel. Subsequently, we analysed whether the increase in water river temperature during summer could account for the observed results. To that end, we acclimated juvenile sturgeons to mild (18 °C) or warm (24 °C) temperatures for 37 days. Like in summer, sturgeons exposed to 24 °C showed lower levels of serum ACP, Cp and total proteins, together with a progressive decrease in body weight and increased fish mortality. Administration of an immunostimulant containing Se and Zn slightly reverted the temperature-induced effects on sturgeon's defences. Altogether, our study provides novel data on various physiological parameters of the Russian sturgeon and highlights the impact warm temperature has on stress and innate immunity in this chondrostean fish.

Topical ocular dexamethasone decreases intraocular pressure and body weight in rats.

BackgroundRecently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats.ResultsTen-week old Sprague Dawley (SD) rats (N = 12) were used to evaluate the effect of topical 0.1 % dexamethasone (50 μl) administered 3 times daily for 4 weeks. Sodium chloride (0.9 %) was used in another group of rats (N = 12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3 ± 1.3 mmHg in the treated eyes, compared to 14.8 ± 2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P = 0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P < 0.001) and alanine transaminase (P = 0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment.ConclusionsIn contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose.Electronic supplementary materialThe online version of this article (doi:10.1186/s12952-016-0048-x) contains supplementary material, which is available to authorized users.

Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats.

Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three-month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days.

Estimation of normal hydration in dialysis patients using whole body and calf bioimpedance analysis

Prescription of an appropriate dialysis target weight (dry weight) requires accurate evaluation of the degree of hydration. The aim of this study was to investigate whether a state of normal hydration (DWcBIS) as defined by calf bioimpedance spectroscopy (cBIS) and conventional whole body bioimpedance spectroscopy (wBIS) could be characterized in hemodialysis (HD) patients and normal subjects (NS). wBIS and cBIS were performed in 62 NS (33 m/29 f) and 30 HD patients (16 m/14 f) pre- and post-dialysis treatments to measure extracellular resistance and fluid volume (ECV) by the whole body and calf bioimpedance methods. Normalized calf resistivity (ρN,5) was defined as resistivity at 5 kHz divided by the body mass index. The ratio of wECV to total body water (wECV/TBW) was calculated. Measurements were made at baseline (BL) and at DWcBIS following the progressive reduction of post-HD weight over successive dialysis treatments until the curve of calf extracellular resistance is flattened (stabilization) and the ρN,5 was in the range of NS. Blood pressures were measured pre- and post-HD treatment. ρN,5 in males and females differed significantly in NS. In patients, ρN,5 notably increased with progressive decrease in body weight, and systolic blood pressure significantly decreased pre- and post-HD between BL and DWcBIS respectively. Although wECV/TBW decreased between BL and DWcBIS, the percentage of change in wECV/TBW was significantly less than that in ρN,5 (−5.21 ± 3.2% versus 28 ± 27%, p < 0.001). This establishes the use of ρN,5 as a new comparator allowing a clinician to incrementally monitor removal of extracellular fluid from patients over the course of dialysis treatments. The conventional whole body technique using wECV/TBW was less sensitive than the use of ρN,5 to measure differences in body hydration between BL and DWcBIS.

Weight gradient and physiological responses to cation-treatment by &lt;i&gt;Salmonella enterica&lt;/i&gt;-infected rabbits

Interest in immunomodulators is increasing following the recognition that positive immunomodulators could be useful intervention tools in the control of diseases and infections. An attempt to determine the effects of some of the cations on body weight and physiological reactions was carried out. Thirty five female adult New Zealand white rabbits grouped into seven, 5 pairs per each of these cations (Zn 2+, Cu 2+ and Mg 2+ ), and supplemented with 1ml/day of single and double strength concentrations of cation for 24 days; the control was not supplemented with any cation. During the study period the rabbits were fed with Guinea grower mash and water ad libitum. There was regular taking of body weight of the rabbits using a top- loading weighing balance, while feed consumption, rectal temperature, stool frequency, physical appearance and behavioural changes were noted. Weight gradient studies show gradual increase in body weight following cation treatment of rabbits, but after challenging the various groups with oral administration of 0.5 ml of 10 6 CFU / ml of saline suspension of Salmonella. enterica for three exposures on alternative days, there was a progressive decrease in body weight of rabbits. However, there was no significant difference in stool dropping, body weakness, dullness and rough furs in all the groups. Effects were more pronounced in control group than in cation supplemented groups. This result, therefore, provide evidence of the significance of zinc, copper and magnesium oral supplementation in mammals and, of course among these three cations, copper appears to be more effective in improving body weight gain, though the mechanism is not known.Keyword: Trace elements, Body weight, Physiological responses, Salmonella entericadoi: 10.4314/ajcem.v12i3.2

Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat

To investigate the anti-obesity effect of the adipokine zinc-α(2)-glycoprotein (ZAG) in rats and the mechanism of this effect. Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 μg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. These results show that ZAG produces increased lipid mobilization and utilization in the rat.

Assessment of degree of hydration in dialysis patients using whole body and calf bioimpedance analysis

Prescription of an appropriate post hemodialysis (HD) dialysis target weight requires accurate evaluation of the degree of hydration. The aim of this study was to investigate whether a state of normal hydration as defined by calf bioimpedance spectroscopy (cBIS) could be characterized in HD and normal subjects (NS). cBIS was performed in 62 NS (33 m/29 f) and 30 HD patients (16 m /14 f) pre- and post-dialysis to measure extracellular resistance. Normalized calf resistivity at 5 kHz (ρN,5) was defined as resistivity divided by body mass index. Measurements were made at baseline (BL) and at a state of normal hydration (NH) established following the progressive reduction of post-HD weight over successive dialysis treatments until the ρN,5 was in the range of NS. Blood pressures were measured pre- and post-HD treatment. ρN,5 in males and females differed significantly in NS (20.5±1.99 vs 21.7±2.6 10-2 Ωm3/kg, p>0.05). In patients, ρN,5 notably increased and reached NH range due to progressive decrease in body weight, and systolic blood pressure (SBP) significantly decreased pre- and post-HD between BL and NBH respectively. This establishes the use of ρN,5 as a new comparator allowing the clinician to incrementally monitor the effect of removal of extracellular fluid from patients over a course of dialysis treatments.

Impaired growth hormone-releasing hormone neurons ultrastructure and peptide accumulation in the arcuate nucleus of mosaic mice with altered copper metabolism

A progressive decrease in body weight and retarded linear growth observed in mosaic male mice with the mutation linked to X-chromosome (Atp7a mo−ms) raised the question whether hypophysiotropic growth axis activity may be affected in these animals. A pathologically developed median eminence ultrastructure with very low somatostatin accumulation as well as an intensive phagocytosis of growth hormone cells observed in the anterior pituitary gland raised the question whether hypothalamic growth hormone-releasing hormone (GHRH) neuronal network is also affected in mosaic mice. In this study an arcuate nucleus GHRH neurons ultrastructure as well as GHRH peptide accumulation in normal and mutant mice were compared. An electron microscopic immunocytochemical method with colloidal-gold labeling was applied to compare the ultrastructural morphology of GHRH neuron and intracellular GHRH peptide distribution. Mosaic mice exhibited a pathologically developed ultrastructure of arcuate nucleus GHRH neurons, defective intracellular peptide localization as well as reduced peptide storage. Obtained results support the crucial role of unaltered copper metabolism in physiological development of hypophysiotropic growth axis activity. Consequently, a pathologically developed GHRH hypothalamic network may impact progressive decrease in body weight and retarded length growth observed in mosaic male mice.

Changes in Glucagon-like Peptide-1 (GLP-1) Secretion after Biliopancreatic Diversion or Vertical Banded Gastroplasty in Obese Subjects

Bariatric operations promote weight loss and improve glucose homeostasis. Glucagon-like peptide-1 (GLP-1) is considered as a possible mediator of the antidiabetic effects of such operations. The present study aimed to gain information on the time course for changes in glucose tolerance, as well as insulin, glucagon and GLP-1 secretion, during an oral glucose tolerance test (OGTT), in 31 obese patients examined 1, 3 and 6 months after Larrad's biliopancreatic diversion (BPD) or 6 months after vertical banded gastroplasty (VBG). A time-related progressive decrease in body weight coincided with lowering of plasma triglycerides, decrease of basal plasma glucose and its incremental area during OGTT, and reduction of basal plasma insulin together with an increase of its incremental area. The time-related decrease of plasma glucagon during OGTT was comparable before and after surgery. Both the basal plasma GLP-1 concentration and its incremental area during the OGTT increased strikingly after surgery, a steady-state situation being reached 3 months after surgery. The most striking differences between the somewhat older and less glucose-tolerant subjects of VBG compared to BPD after surgery, consisted in a decrease in cholesterol and LDL only observed in BPD and a much more pronounced increase in basal and incremental plasma GLP-1 in BPD. GLP-1, like glucagon, increased lipolysis, but failed to duplicate the lipogenetic action of insulin in isolated adipocytes obtained at the time of surgery. These findings support the postulated role of GLP-1, secreted by the hindgut, as a key mediator of the antidiabetic effects of bariatric operations.

Efficacy and safety of torsemide in patients with moderate congestive heart failure

A multicenter open-label study was conducted to evaluate the efficacy and safety of torsemide in 170 patients with New York Heart Association (NYHA) Class II to Class III congestive heart failure (CHF). Patients were assigned to receive torsemide for 2 months starting at 10 mg/d, to be adjusted after 14 or 30 days according to the diuretic effect and overall clinical condition of the individual. NYHA class, body weight, ankle circumference, blood pressure, heart rate, degree of dyspnea, and signs and symptoms of CHF were recorded monthly. Safety was evaluated by recording adverse events during the study and by monitoring electrocardiographic tracings and laboratory test results. All 170 study patients were eligible for the safety analysis, 150 of whom were included in the efficacy (perprotocol) analysis. Statistically significant changes in fluid mobilization with a progressive decrease in body weight and marked reduction of peripheral edema were observed. Functional status (NYHA class) improved in 66 patients (44%), and a lower degree of dyspnea, based on the World Health Organization classification, was detected in 98 patients (65.3%), with nocturnal coughing and pulmonary rales resolving in 30 of 34 and 81 of 87 patients, respectively. Torsemide did not significantly affect carbohydrate or lipid metabolism or serum electrolyte levels. Fourteen adverse events were reported for 9 patients (5.3%). Two of the 9 patients discontinued treatment, 1 because of persistent left ventricular failure and multiple episodes of dizziness and 1 because of hospitalization for suspected hepatoma. One patient with persistent dizziness, increased sweating, and asthenia required a dose change; the symptoms resolved after the dose was reduced. Results of this study suggest that torsemide was well tolerated and effective in the treatment of moderate CHF.