Auranofin attenuates Schistosoma mansoni egg-induced liver granuloma and fibrosis in mice.

Schistosomiasis is a serious tropical disease. Despite extensive research into the etiology of liver fibrosis, effective therapeutic options remain limited. This study aims to assess the effectiveness of auranofin in treating hepatic granuloma and fibrogenesis produced by Schistosoma (S.) mansoni eggs. Auranofin is a gold complex that contains thioglucose tetraacetate and triethylphosphine. Eighty BALB/c male mice were divided into four groups (n=20/group): negative control (GI), positive control (GII), and early (GIII) and late (GIV) treatment groups with oral auranofin according to beginning of treatment 4th week and 6th week post-infection. Mice were infected subcutaneously in a dose of 60±10 cercariae/mouse. Worm counts, egg loads, and oogram patterns were determined. Biochemical, histological, and immunostaining of interleukin-1ß (IL-1ß), Sirtuin 3 (SIRT3), and smooth muscle actin (SMA) were assessed. GIII showed a significant decrease in the total S. mansoni worm burden and ova/gram in liver tissue (with reduction percent of 63.07% and 78.26%, respectively). Schistosomal oogram patterns, immature and mature ova, also showed a significant decrease. The reduction in granuloma number and size was 40.63% and 48.66%, respectively, in GIII, whereas in GIV, the reduction percent was 76.63% and 67.08%. In addition, the degree of fibrosis was significantly diminished in both treated groups. GIV showed significant reduction in IL-1ß and SMA expression and increase in SIRT3 expression. These findings reveal how auranofin suppresses the development of liver fibrosis. Therefore, it is crucial to take another look at auranofin as a prospective medication for the treatment of S. mansoni egg-induced hepatic granuloma and consequent fibrosis.

Treatment Trial of Nile Tilapia (Oreochromis niloticus) Experimentally Infected with Vibrio alginolyticus Isolated from Sea bass (Dicentrarchus labrax).

BACKGROUND AND OBJECTIVE: In Egypt, Nile tilapia represents the main cultured type due to its economical price, palatability and easy culturing. This study was aimed to elucidate the pathogenicity of V. alginolyticus isolated from diseased sea bass and experimentally infected healthy Nile tilapia fish. MATERIALS AND METHODS: Healthy Nile tilapia fish were injected I/P with V. alginolyticus isolated from diseased sea bass. Symptoms and mortality rates of infected Nile tilapia fish were recorded during the experimental period. Re-isolation of V. alginolyticus was done from infected tilapia fish by bacteriological methods. For confirmation the pathogenicity of Vibrio isolated either from marine fish or tilapia fish, PCR test was done using tdh and bla gens. Liver and kidney function tests with histopathological examinations of some organs were performed. Treatment trial was done according to the antibiotic sensitivity test. RESULTS: The isolated Vibrio is highly pathogenic to Nile tilapia fish causing deterioration in all parameters which finished by severe mortalities. Treatment with florfenicol, enrofloxacin, or oxytetracycline reduced the mortality rate and improved liver and kidney function parameters of infected Nile tilapia fish. CONCLUSION: V. alginolyticus can infect both marine and fresh water fish inducing a high mortality rate. Treatment of infected fish with florfenicol, enrofloxacin, or oxytetracycline reduces the mortality rate.

Epidemiological and molecular investigation of resurgent cutaneous leishmaniasis in Sudan.

OBJECTIVES: Local health personnel have drawn attention to an apparent increase in incidence and severity of cutaneous leishmaniasis (CL) in Sudan. The objective of this study was to investigate CL burden and surveillance. METHODS: Surveillance data were compiled from the KalaCORE programme, Leishmania coordinators in Northern Kordofan and Southern Darfur, and Khartoum Dermatology Hospital. CL lesions were sampled from 14 suspected cases from Northern Kordofan and the Hospital for Tropical Diseases in Omdurman. PCR-restriction fragment length polymorphism analysis and multilocus sequencing were used to characterize the disease agent. RESULTS: All sites reported substantial increases from 2014 to 2016/7, far exceeding World Health Organization case reports for 2014, consistent with a widespread outbreak. Single seasonal peak incidence was observed, except for two peaks in Southern Darfur. In Northern Kordofan, the odds ratio for CL in the 35-44 years age group was 2.6 times higher than in the >45 years age group (p<0.0001); in Southern Darfur, the OR was 2.38 greater in males than females (p<0.0001). Lesions included severe presentations, despite chemotherapy. Leishmania major was identified as the agent. CONCLUSIONS: Active surveillance is required to understand the extent of CL in Sudan, as well as training to standardize surveillance, diagnosis, reporting, and quality control. Point-of-care rapid diagnosis would be valuable. Genotyping and phenotyping are required to monitor the emergence of pathogenic strains, drug resistance, outbreaks, and changes in severity.

Effects of Callistemon citrinus aqueous extract on prepatent and patent infections with Schistosoma mansoni in experimentally infected mice.

Schistosomiasis is a chronic debilitating parasitic disease that causes hepatic damage and is known to be endemic in developing countries. Recent control strategies for schistosomiasis depend exclusively on chemotherapeutic agents, specifically praziquantel. Unfortunately, praziquantel has low efficacy in the early phase of infection, and resistance to treatment is increasingly reported. The aim of this work was to find an alternative treatment by assessing the in vivo activity of aqueous extract of Callistemon citrinus against Schistosoma mansoni in both prepatent and patent phases in experimentally infected mice. The study was conducted on 80 male BALB/c albino mice divided into eight groups. Callistemon was administered at a dose of 200 mg/kg on days 14 and 45 post infection as a single therapy and in combination with praziquantel. Porto-mesenteric worm burden, hepatic and intestinal egg counts, hepatic granuloma number and diameter, and oogram pattern were assessed to evaluate the anti-schistosomal properties of C. citrinus. Liver enzymes and total bilirubin were tested to assess hepatoprotective effects. Results revealed that the use of C. citrinus was associated with a significant decrease in worm burden and tissue egg load together with an increased percentage of dead eggs. In addition, there was a significant reduction in granuloma formation. Callistemon also led to a significant improvement in liver function. The best results were obtained when C. citrinus was given in the prepatent phase of infection and when combined with praziquantel. Although the effects of C. citrinus are considered to be promising, further studies using different extracts, active ingredients and doses are needed.

Preliminary study on association of beta2-adrenergic receptor polymorphism with hypertension in hypertensive subjects attending Balok Health Centre, Kuantan.

Polymorphisms within the beta2-adrenergic receptor (ADRB2) gene have been repeatedly linked to hypertension. Among the ADRB2 polymorphisms detected, Arg16Gly and Gln27Glu codons are considered the two most important variations. The amino acid substitution at these codons may lead to abnormal regulation of ADRB2 activity. The aim of the present study was to assess the association between ADRB2 polymorphisms and hypertension. This case-control study consisted of 100 unrelated subjects (50 hypertensive and 50 matched normal controls). Arg16Gly and the Gln27Glu polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. There were no significant evidence of association in allelic and genotypes distribution of Arg16Gly and Glu27Gln with blood pressure and hypertension. These findings suggest that the variation within codon 16 and 27 of ADRB2 gene were unlikely to confer genetic susceptibility for hypertension in our population samples.

Differential response to salinity and water deficit stress in Polypogon monspeliensis (L.) Desf. provenances during germination.

The effects of provenance, salinity (0, 100, 200, 300 and 400 mm NaCl) and water deficit (0, -0.6, -1.1, -1.6 and -2.1 MPa mannitol solutions) on germination success of Polypogon monspeliensis were investigated. Eight Tunisian provenances from different bioclimatic origins were considered. Seed mass varied significantly between populations. Germination percentage was significantly affected by provenance, salinity and their interaction. Even at 300 mm NaCl, germination percentage of Tabarka, Kelbia and Kebili ranged from ca. 60% to ca. 85%, whereas Monastir, Gabes and El Haouaria succeeded in germinating in 200 mm NaCl. The 300 mm NaCl treatment highly reduced germination of Monastir and El Haouaria, and inhibited that of Gabes. Soliman and El Jem were the least salt-tolerant provenances. The severity of water deficit impact on seed germination was also provenance-dependent, especially at osmotic potentials of -1.1 to -1.6 MPa. At -1.6 MPa, germination percentage of Tabarka, Monastir and Kebili was close to 80%, while that of Gabes, El Jem and Kelbia was 0%, 5% and 20%, respectively. Regardless of provenance, germination was strongly impaired at -2.1 MPa. The variability of stress tolerance in P. monspeliensis could be of practical significance in programmes aimed at restoring arid and salt-affected lands since it allows use of provenances that germinate and establish successfully under unfavourable conditions prevailing in such zones.

Treatment of cholera-like diarrhoea with oral rehydration.

Cholera diarrhoea remains a major global health problem that has caused seven pandemics. The pathogenesis of cholera is attributable to the production of cholera toxin by the causative pathogen, Vibrio cholerae. The toxin causes increased production of cyclic adenosine monophosphate and this results in massive water and electrolyte secretion into the intestinal lumen. These changes manifest clinically as the painless defecation of voluminous stools that resemble 'rice water', leading to severe dehydration. The cornerstone in the management of cholera diarrhoea is the use of oral rehydration solutions (ORS) to replace the water and electrolytes lost as stools. The World Health Organization recommends the use of ORS of 'reduced osmolarity' for the treatment of acute non-cholera diarrhoea and the use of rice-based ORS for the management of cholera diarrhoea. Although several attempts have been made to improve ORS, studies to evaluate some of the modifications, which include the addition of amylase-resistant starch, the use of amino acids (such as glycine, alanine and glutamine) as sodium cotransporters, and zinc-supplemented ORS, are still needed.

Interactive effects of salinity, nitrate, light, and seed weight on the germination of the halophyte Crithmum maritimum.

Interaction of salinity, nitrate, light, and seed weight on the germination of Crithmum maritimum was investigated. Seeds of three size categories were germinated at 0-200 mM NaCl with either 0, 5 or 20 mM KNO 3 . Experiments were done under darkness, white light, or red light. Regardless of seed weight, germination was maximal in distilled water. Under salinity, the smallest seeds showed the highest germination percentage. Salt impact was amplified by darkness, but was mitigated by nitrate supply, red light and their combination. At the same PPFD, germination of T2 seeds was higher, when exposed to red light than under white light, suggesting that germination was more influenced by the light type than by the PPFD. As a whole, not only salinity, nutrient availability, seed weight, and light, but also their interaction may control the germination of this halophyte.

Loss of Fhit protein expression in high-grade and advanced stage endometrial carcinomas.

BACKGROUND: The fragile histidine triad (FHIT) gene is a candidate tumor suppressor gene located at 3p14.2, and the absence or reduction of Fhit protein expression has recently been reported in various carcinomas. MATERIALS AND METHODS: We examined the expression of Fhit protein in 50 endometrial carcinomas and 19 normal endometrial tissues by immunohistochemistry, and this expression was correlated with clinicopathological parameters, p53 expression, sex steroid receptor status and abnormal FHIT transcripts. RESULTS: All the specimens of normal endometrial gland in the proliferative phase exhibited relatively strong Fhit expression, while most of endometrial tissues in the secretory phase showed weak Fhit expression. In 50 endometrial carcinomas, immunoreactivity for Fhit protein was strong in 21 cases (42%), weak in 22 cases (44%) and partially or totally absent in the remaining 7 cases (14%). There were significant correlations of negative Fhit expression with high tumor grade (p = 0.033) and with advanced stage (p = 0.048). On the other hand, abnormal FHIT transcripts lacking several exons were found in 29% of cases. Neither p53 nor sex steroid receptor status were significantly related with the loss of Fhit expression. CONCLUSION: The loss of Fhit protein expression may be associated with aggressive phenotype of endometrial carcinomas.

Expression of cold-inducible RNA-binding protein in the normal endometrium, endometrial hyperplasia, and endometrial carcinoma.

Cold-inducible RNA-binding protein (CIRP), an 18-kD protein in the mouse and human, is induced by lowering the temperature of cultured cells. CIRP is possibly a cell cycle regulator because its overexpression results in prolongation of G1 phase in vitro. We investigated the immunohistochemical expression of CIRP in 39 endometrial carcinomas, 12 endometrial hyperplasias, and 27 normal endometria using polyclonal antibody against CIRP and confirmed by Western blot analysis. CIRP was localized in the nuclei of glandular, stromal, and endothelial cells. The intensity of CIRP expression in glandular cells during the menstrual cycle was inversely proportional to its proliferative (Ki-67) activity, whereas it remained unchanged in stromal and vascular endothelial cells. The intensity of CIRP expression in hyperplastic glands was variable, whereas CIRP expression was absent or markedly reduced in most of the endometrial carcinomas. These results suggest that CIRP may participate in the cell cycle regulation of normal endometrium and the loss of its expression may be involved in endometrial carcinogenesis.

Cyclical change of hMSH2 protein expression in normal endometrium during the menstrual cycle and its overexpression in endometrial hyperplasia and sporadic endometrial carcinoma.

BACKGROUND: The role of hMSH2 protein, one of the major DNA repair proteins, until now, had not been elucidated in terms of normal endometrial function during the menstrual cycle. The current study was designed to address this issue and to determine whether the expression of hMSH2 is altered in the course of endometrial carcinogenesis. METHODS: Immunohistochemical reactivity with a monoclonal antibody against the hMSH2 protein was examined in endometrial tissue specimens from 45 patients with normal endometrium, 51 patients with endometrial hyperplasia, and 27 patients with endometrial carcinoma. Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) also was studied in the same samples as a measure of the proliferative activity and was compared with hMSH2 expression in each sample. RESULTS: The functional layer of normal endometrium displayed cyclic changes in hMSH2 protein expression during the menstrual cycle, showing positive expression in the proliferative phase and becoming weak to negative in the secretory phase. This expression pattern was similar to that of PCNA. Sixty-three percent of endometrial carcinomas showed strong positivity for both hMSH2 and PCNA expression, and 7.4% had an intensity of hMSH2 protein expression similar to that found in normal proliferative endometrial glandular cells. There was only 1 sample (3.7%) that was completely negative for hMSH2 expression, and 26% of samples were weakly positive for PCNA and hMSH2 protein. All simple hyperplasias and the majority of complex and atypical hyperplasias showed positive immunoreactivity for hMSH2 and PCNA. CONCLUSIONS: This study demonstrates that hMSH2 protein expression changes during the menstrual cycle in parallel with proliferative activity. In most patients with sporadic endometrial carcinoma, the expression of hMSH2 protein is consistent with PCNA expression. In contrast, loss of hMSH2 expression is observed rarely in patients with sporadic endometrial carcinoma.