Behavioural Effects of the Methanolic Root Bark Extract of Securinega Virosa in Rodents

Securinega virosa is used traditionally as sedative in children and in mental illnesses. In this study, the behavioral effects of methanolic root bark extract of S. virosa were investigated in mice. The results revealed that the extract significantly (P<0.05) and dose-dependently reduced the onset and prolonged the duration of sleep. The extract significantly (P<0.05) decreased exploratory activity and reduced the rate of apomorphine-induced stereotyped climbing at the doses tested (6.25–25mg/kg). It also produced a significant and dose-dependent motor coordination deficit in mice at the doses tested (P<0.01). The intraperitoneal median lethal dose in mice was 774.6mg/kg while the preliminary phytochemical screening revealed the presence of alkaloids, tannins, saponins and flavonoids. These results suggest that methanolic root bark extract of S. virosa contains biologically active principles that are sedative in nature and lend pharmacological credence to the ethnomedical use of the plant.     

The Fawn-Hooded (FH/Wjd) rat: a genetic animal model of comorbid depression and alcoholism

The Fawn-Hooded (FH/Wjd) rat is an inbred strain of rat that has been reported to exhibit both high immobility in the forced swim test and high voluntary ethanol intake, measures that have been periodically linked with depression and alcoholism in humans. The present paper will first present a survey of the literature and previously unpublished findings that bear on the question of whether FH/Wjd rats should be considered genetic animal models of depression and alcoholism. Subsequently, behavioral studies of the FH/Wjd rats, the non-drinking ACI/N strain, and their F1 and F2 intercrosses will be described. Under free choice conditions, the FH/Wjd rat drinks up to 6 g/kg 10% ethanol per day. This intake was sufficient to render the rats tolerant to the hypothermic effects of injected ethanol (2.5 g/kg). Rats that had been voluntarily drinking for at least 6 weeks also exhibited withdrawal-induced anxiety in the social interaction, elevated plus maze, and ultrasonic vocalization tasks. The FH/Wjd rat exhibits a 25-30% increase in alcohol intake when the alcohol is returned after a 24-h period of deprivation. It responds to drugs that are effective in humans with a reduction in alcohol intake. Therefore, the FH/Wjd rat meets most of the criteria for an animal model of alcoholism. Chronic antidepressant treatments correct several of the abnormalities exhibited by the FH/Wjd rats, including the exaggerated immobility in the forced swim test. Therefore, the FH/Wjd rats also fulfill some of the criteria for an animal model of depression. On the contrary, inbred ACI/N rats do not drink much alcohol voluntarily and are quite active in the forced swim test. The FH/Wjd and ACI/N rats were intercrossed to obtain the F1 and F2 progenies, which were then tested for alcohol intake and immobility. Alcohol intake and immobility were distributed in different patterns in the F1 and F2 progenies. Alcohol intake was intermediate in the F1 progeny, while immobility was closer to the FH/Wjd parents. In the F2 progeny, chi-square analyses indicated that the distributions were significantly different. In addition, there were no significant litter effects, indicating that maternal effects did not appear to occur. There were also no significant differences among rats with different coat colors, suggesting that the Fawn-Hooded phenotype can be separated from the measures of alcohol intake and immobility. We conclude that the FH/Wjd rat is a genetic animal model of depression and alcoholism, but that the two measures reflective of these states are under separate genetic controls.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Separation of graft-vs.-tumor effects from graft-vs.-host disease in allogeneic hematopoietic cell transplantation

Allogeneic hematopoietic cell transplantation (HCT) is an increasingly widely used treatment modality in hematological malignancies. Alloreactivity mediated by donor T cells (and, in some settings, by donor natural killer cells) can produce durable immunologic control or eradication of residual malignancy after allogeneic HCT. However, graft-vs.-tumor (GVT) effects are variably effective and are often accompanied by deleterious alloreactivity against normal host tissue, manifesting as graft-vs.-host disease (GVHD). A major focus of current research in HCT is the separation of beneficial GVT effects from GVHD. Here we review a number of approaches currently under investigation to specifically augment GVT effects, including the identification of minor histocompatibility antigens (mHA), adoptive immunotherapy with tumor-specific or mHA-specific cytotoxic T lymphocytes, vaccination of the donor or recipient to stimulate tumor-specific immunity, and adoptive transfer of natural killer cells. In addition, we review strategies being investigated to specifically suppress GVHD while sparing GVT, including the manipulation and infusion of regulatory T cells, the use of novel pharmacologic and biologic agents, and the use of mesenchymal stem cells. Ultimately, advances in separation of GVT from GVHD will further enhance the potential of allogeneic HCT as a curative treatment for hematological malignancies.     

Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.     

Membrane expression of platelet calpain

Platelet calpain has many platelet substrates, including external membrane proteins. We thus investigated whether platelet calpain II was associated with platelet membranes in unstimulated and thrombin- activated platelets. A monospecific, goat polyclonal antibody was reared to purified platelet calpain II. Sixteen whole platelet lysates were found to contain 4.5 +/- 0.7 micrograms calpain antigen II per 10(8) platelets (mean +/- SEM) as determined by a competitive enzyme- linked immunosorbent assay. Using the dipeptide fluorogenic substrate, Suc-Leu-Tyr-MCA, 17 human platelet lysates contained 3.6 +/- 0.4 micrograms calpain activity per 10(8) platelets. Platelet calpain II was associated with the Triton X-100 insoluble platelet cytoskeletons from both unstimulated and thrombin-activated platelets. When compared with the total cell content of platelet calpain II, calpain antigen (10% to 13%) and calpain activity (24% to 28%) was associated with platelet cytoskeletons in unstimulated and thrombin-activated platelets, respectively. On immunoblot, the heavy chain (80 Kd) of calpain II was detected in platelet cytoskeletons. Subcellular fractionation studies on both unstimulated and thrombin-activated platelets, revealed that half of the total platelet calpain II antigen was associated with cytosol, and the other half was associated with the membrane fraction. Platelet calpain II was not seen on the surface of unstimulated, paraformaldehyde fixed platelets by immunofluorescence. However, on thrombin-activated platelets, rim immunofluorescence was seen, indicating that activated platelets externalize their calpain. This observation was confirmed by the finding that about 2,000 molecules per platelet of an 125I-anti-calpain II Fab' specifically bound to thrombin-activated but not unstimulated platelets. Both dibucaine (1 mmol/L) and platelet activating factor (1.86 mumol/L) in the absence of external Ca++, but not collagen (5 micrograms/mL) or ionophore A23187 (2.5 mumol/L) in the absence of external Ca++, were also able to externalize platelet calpain II antigen, as indicated by a similar level of specific 125I-anti-calpain II Fab'-platelet binding. These combined studies indicate that platelet calpain II is a major protein, comprising 2% of total platelet protein, a substantial portion of which is membrane-associated. When platelets are activated by thrombin and platelet activating factor, calpain II antigen also becomes present on the external platelet surface.     

Comparison between Gallbladder Serosal and Mucosal Patch in Duodenal Injuries Repair in Dogs

Background: One of the most challenging problems in clinical surgery is management of an extensive duodenal injury. In its management, there are limitations in using jejunal serosal patch and other conventional methods in specific conditions. This study was performed to compare treatment of large duodenal defects by a gallbladder serosal patch and the gallbladder mucosal patch in a dog as an animal model. Methods: A duodenal defect (2 cm, about 50% of the total circumference) was created in the second portion of the duodenum in eight dogs. The animals were divided into two equal groups, with group 1 undergoing serosal patch repair and group 2 undergoing mucosal patch repair. The macroscopic and microscopic healing features of the gallbladder serosal and mucosal patch were compared. Results: None of the dogs died due to surgical complications. The whole grafted area was covered by neomucosa at the end of the third week in all animals with the gallbladder serosal patch (group 1). In this group, the scar was small; no significant narrowing of lumen was noted and serosal healing was uniformly complete. In histological examination, a complete coverage of the gallbladder serosal patch by neomucosa consisting of columnar epithelium with short villous formations was observed. In mucosal patch models (group 2), complete epitheliazation, mild fibrosis, and incomplete repair were visible. In histological examination, severe inflammation was noticed too. Conclusion: In patients with multiple trauma affecting upper gastrointestinal tracts, use of the gallbladder serosal patch method is easy and reliable. So it may be considered in the surgical management of large duodenal defects, which cannot be repaired by available conventional methods.     

Predictors of Weight Regain and Insufficient Weight Loss According to Different Definitions After Sleeve Gastrectomy: a Retrospective Analytical Study

Background

Weight regain (WR) and insufficient weight loss (IWL) after sleeve gastrectomy (SG) are challenging issues. This study aimed to evaluate the predictors of WR and IWL after SG.

Methods

In this retrospective analytical study, 568 patients who underwent SG at Hazrat-e Rasool General Hospital, Tehran, Iran, between January 2015 and April 2022 were evaluated. A total of 333 patients were included. WR and IWL were evaluated by multiple criteria such as a BMI of > 35 kg/m², an increase in BMI of > 5 kg/m² above nadir, an increase in weight of > 10 kg above nadir, percentage of excess weight loss (%EWL) < 50% at 18 months, an increase in weight of > 25% of EWL from nadir at 36 months, and percentage of total weight loss (%TWL) < 20% at 36 months. All participants were followed up for 36 months.

Result

The univariate analysis showed that preoperative BMI, obstructive sleep apnea, metformin consumption, and grades 2 and 3 fatty liver disease were associated with WR and IWL (P < 0.05). WR or IWL incidence varied (0–19.3%) based on different definitions. The multivariate analysis showed that a preoperative BMI of > 45 kg/m² [odds ratio_Adjusted (OR_Adj) 1.77, 95% CI: 1.12–4.11, P = 0.038] and metformin consumption [OR_Adj: 0.48, 95% CI: 0.19–0.78, P = 0.001] were associated with WR and IWL after SG, regardless of the definition of WR or IWL.

Conclusion

This study showed that preoperative BMI of > 45 kg/m², obstructive sleep apnea, metformin consumption, and grades 2 and 3 of fatty liver disease were associated with WR or IWL.

Graphical abstract

     

Cross-education of muscle strength: cross-training effects are not confined to untrained contralateral homologous muscle

The aim of this study was to evaluate whether electrical muscle stimulation (EMS) on dominant wrist flexors causes an increase in the muscle strength of the contralateral wrist extensors. Twenty-three healthy, young, adult men were included in this prospective, double-blind, controlled study. Participants were randomly allocated to the EMS group or Control group. Electrodes were placed over the flexor aspect of the right forearm in both groups. In the EMS group, passive wrist extension and (EMS) that caused powerful muscle contraction were simultaneously applied. In the Control group, a conventional mode of transcutaneous electrical nerve stimulation was applied without causing any contraction. A group effect (P=0.0001) and group-by-time interaction were found (P=0.0001) for both the wrist flexor and extensor muscles, but not group-by-time-by-arm interactions. This implies that the effect of the interventions was similar in both arms, but that the response was significantly larger in the EMS than in the Control group. The results of the current study suggest that cross-education is not confined to the untrained contralateral wrist flexors and that the strength increase may also be observed in the contralateral wrist extensors.