POTENTIAL IMPACT OF COQ10 AND VITAMIN E AGAINST (STZ) INDUCED METABOLIC DETERIORATION IN THE ALBINO RATS

Objective: This study evaluates the hypoglycemic effect of COQ10 and Vitamin E are determined using STZ induced diabetic rats.Methods: Rats selected for this study were divided into five groups of ten rats each as follows: first group Normal control rats, the second is considered as diabetic groups, injected intraperitoneal with a single dose of STZ (60 mg/kg B. wt). the third group Diabetic rats orally administered glibenclamide drug 10 mg/kg B. wt daily for 30 d 4th. And 5th groups were treated orally glibenclamide combined with vitamin E (2% concentration added to the normal basal diet), or coenzyme Q10 at the dose of 10 mg/kg i. p. daily for 30 consecutive days in addition histological examinations of liver, kidney and brain were carried out to confirm the biochemical changes of the diabetic group of rats.Results: All liver enzymes activities alanine and aspartate transferases and alkaline phosphatase (AST, ALT and ALP respectively), kidney function tests; creatinine and total urea, inflammatory biomarkers; CRP, IL-10 and TNF-α. Neurotransmitters; acetylcholine and acetylcholine esterase were enhanced with the highest degree in groups treated with COQ10 or vitamin E in addition to glibenclamide dug, almost restore the normal histological architecture of liver, kidney and brain.Conclusion: Orally supplemented glibenclamide with coenzyme Q10 or vitamin E showing significantly reduced blood glucose levels in STZ induced diabetic rats. It also showed hypolipidemia as well as hepatoprotective effects, enhance histological feature of liver, kidney and brain.Â

2,4-CYCLOADDITION REACTIONS: PREPARATION AND CYTOTOXICITY OF NOVEL QUINOLINE AND PYRROLO [3,4-f] QUINOLINE DERIVATIVES

Objective: the present work aimed to synthesize novel quinoline and pyrroloquinoline derivatives and study their cytotoxic activity.Methods: Diels–Alder reaction (4+2) was used for the synthesis of new quinolone and pyrrolo quinoline derivatives via the reactions of compound 1 with N-maleimide (4a-d) derivatives, ethyl acrylate (6) methylmethacrylate (8) and acetylene dicarboxylic acid (10). The synthesized compounds were characterized by NMR and Mass spectral data. Some of the synthesized compounds were screened for their antitumor activity against three different cell lines (MCF-7, HepG2 and HCT).Results: The tested compounds exhibited antiproliferative activity against the three different cell lines, especially against MCF-7.Conclusion: New quinoline and pyrroloquinoline derivatives were synthesized starting with 6-methyl-4-phenyl-2-thioxo-5-(4-methylphenylthio)-1,2-dihydropyridine-3-carbonitrile. Two new compounds 3 and 5a were tested for their in vitro antiproliferative activity against MCF-7, HepG2 and HCT cancer cell lines. The result showed that compound 3 exhibited more potent antiproliferative activity than compound 5a in case of MCF-7 and HCT cell lines.Â

The role of losartan and enalapril in the protection against stress-induced gastric mucosal ulceration in rats

Background: Angiotensin II (ANG II) is a stress hormone and its level dramatically increases in the stomach during stress. In addition, it generates reactive oxygen species (ROS) with cellular damage and inflammation. So the aim of this study is to evaluate the mechanism of losartan and enalapril in the prevention of stress-induced gastric ulcer through their action on mucosal prostaglandin (PGs) and antioxidant enzymes and compare between them.Methods: Thirty- six adult male wistar albino rats weighing 180-200 g were divided into 6 groups; n= 6. Groups 1, 2, and 3 were received saline (normal control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks. Groups 4, 5, and 6 were pretreated with saline (ulcer control), losartan (3 mg/kg/day) and enalapril (10 mg/kg/day) i.p respectively for 4 weeks duration. On 29th day, group 4, 5 and 6 were submitted to gastric ulcer by water immersion method, then animals of all groups were sacrificed, stomachs were excised for gross and microscopic examination and determination of the mucosal levels of prostaglandin E2 (PGE2), superoxide dismutase (SOD), nitric oxide (NO) and catalase (CAT).Results: Stress produced gastric ulcer and a significant decrease in all measured gastric parameters compared to normal control group. Pre-treatment of rats with losartan or enalapril decreased the stress-induced alterations in mucosal parameters, but only losartan caused a significant increase in CAT activity in addition.Conclusions: Antagonize the action of ANG II by losartan and enalapril have preventive advantages in stress-induced gastric ulcer and losartan has better influence as it has an additional effect on CAT activity

Seroprevalence of Mycobacterium avium subsp. paratuberculosis in Dairy Cattle in Khartoum State, Sudan

Paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), is a chronic wasting disease mainly of domestic and wild ruminants. It occurs worldwide, causing significant economic losses through decreased productivity, low fertility, increased cull rates and mortality. It is listed by the OIE (World Organization for Animal Health) as a disease of concern to trade in animals. Prevalence of this disease can be studied by detecting anti-MAP antibodies by Enzyme linked immunosorbent Assay (ELISA). The aim of this study was to investigate the current prevalence of MAP infection in cattle in Khartoum State. The overall apparent prevalence of MAP infection was found to be 6.3% and 18.9% at animal and herd levels, respectively. All seropositive animals were cross-bred females of good body condition; most of them (>90%) were >3 years old and >50% were from medium-sized herds in Omdurman. No significant association (p > 0.05) was found between seropositivity and animal herd size. The prevalence of MAP infection in Khartoum State is still low to medium compared to other parts of the world, but it is comparable to those reported from other African countries. Further studies with the view of designing nationwide surveys in domestic ruminants and camels in other states of the country are needed for establishing control programmes

Levels of certain tumor markers as differential factors between bilharzial and non-biharzial bladder cancer among Egyptian patients

<p>Abstract</p> <p>Background/Objective</p> <p>Bladder cancer is the commonest type of malignant tumors as a result of schistosomaisis which is a major healthy problem in many subtropical developing countries. The aim of this study is to comparatively elucidate the underlying biochemical tumor markers in schistosomal bladder cancer versus non-schistosomal bladder cancer when compared to normal healthy ones.</p> <p>Methods</p> <p>This work was performed on tissue specimens from total 25 patients and serum samples from total 30 patients versus ten healthy individuals served as control. The investigated parameters in serum are: xanthine oxidase (XO), fructosamine, lactate dehydrogense (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins, essential and non- essential amino acids profile, hydroxyproline, total immunoglobulin E (IgE) and tumor necrosis factor alpha (TNF-<it>α</it>). In addition, the current investigation also extended to study some markers in tumor bladder tissues including, pyruvate kinase enzyme (PK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).</p> <p>Results</p> <p>Results showed that biharzial bladder cancer patients recored more significant elevation in serum XO, fructosamine, LDH, AST, ALT, hydroxyproline, IgE and TNF-<it>α </it>than in bladder cancer patients when compared to control ones. While, in tissues there were significant increase in PK, LDH, AST & ALT activities of schistosomal bladder cancer than in bladder cancer as compared to control healthy patients.</p> <p>Conclusions</p> <p>It could be concluded that, bilharzial and non-bilharzial bladder cancer showed distinct biochemical profile of tumor development and progression which can be taken into consideration in diagnosis of bladder cancer.</p

Protection of mice against experimental infection wild Brucella abortus strain by vaccination via oral and intraperitoneal routes with Brucella abortus RB51

The study was designed to detect the effect of an oral and intraperitoneal (I/P) immunization of mice with B. Abortus RB51 to protect mice against a wild strain of B. abortus I/P challenge infection. Three groups of mice were used in this study. The first group (1st G) immunized with 108 *2 CFU of B. Abortus RB51 intraperitoneally (I/P). The second group (2nd G) immunized orally with 108 *2 CFU dose (Ten minutes prior immunization, all mice were drenched with 0.2 ml of 10% sodium bicarbonate to neutralize gastric acidity). Whereas, the third group (3rdgroup) inoculated with 0.2 ml phosphate buffer saline (PBS) and acted as the control group. The results indicated that there was a significant difference (P<0.05) in antibody titer at 5th week in the I/P group and in the 3rd week in oral group, while there was no significance between the two route through all the periods. However, after the challenge, the antibody titer raised to 0.84±0.11 and 1.14±0.11 in the two route and control group in 3rd and 7th day post challenge respectively. The Ab titer reached 1.44±0.11 in the I/P route and remain at 1.14±0.11 in oral and control at 10th day/post-challenge. The oral inoculation gave a mild infection, which was cleared at 5th week after infection, and it induced a humoral response. However, I/P challenge gave moderate infection, which was cleared at 6th week after infection. Wild B. Abortus was isolated at a lowest level after the challenge from internal organs, in animals immunized I/P compared with the other two groups. In conclusion, I/P and oral immunization were able to give protection against the virulent wild strain B. abortus in mice. Besides, the probability of these mice in transmitting the vaccine to other animals was low and vaccine was safety in pregnant vaccinated mice

Paratuberculosis: The Hidden Killer of Small Ruminants

Paratuberculosis (PTB) is a contagious and chronic enteric disease of ruminants and many non-ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), and is characterised by diarrhoea and progressive emaciation with consequent serious economic losses due to death, early culling, and reduced productivity. In addition, indirect economic losses may arise from trade restrictions. Besides being a production limiting disease, PTB is a potential zoonosis; MAP has been isolated from Crohn’s disease patients and was associated with other human diseases, such as rheumatoid arthritis, Hashimoto’s thyroiditis, Type 1 diabetes, and multiple sclerosis. Paratuberculosis in sheep and goats may be globally distributed though information on the prevalence and economic impact in many developing countries seem to be scanty. Goats are more susceptible to infection than sheep and both species are likely to develop the clinical disease. Ingestion of feed and water contaminated with faeces of MAP-positive animals is the common route of infection, which then spreads horizontally and vertically. In African countries, PTB has been described as a “neglected disease”, and in small ruminants, which support the livelihood of people in rural areas and poor communities, the disease was rarely reported. Prevention and control of small ruminants’ PTB is difficult because diagnostic assays demonstrate poor sensitivity early in the disease process, in addition to the difficulties in identifying subclinically infected animals. Further studies are needed to provide more insight on molecular epidemiology, transmission, and impact on other animals or humans, socio-economic aspects, prevention and control of small ruminant PTB

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation (RCC1) function in MDA-MB-231 breast cancer cells

Ran is a small ras-related GTPase and is highly expressed in aggressive breast carcinoma. Overexpression induces malignant transformation and drives metastatic growth. We have designed a novel series of anti-Ran-GTPase peptides, which prevents Ran hydrolysis and activation, and although they display effectiveness in silico, peptide activity is suboptimal in vitro due to reduced bioavailability and poor delivery. To overcome this drawback, we delivered an anti-Ran-GTPase peptide using encapsulation in PLGA-based nanoparticles (NP). Formulation variables within a double emulsion solvent evaporation technique were controlled to optimise physicochemical properties. NP were spherical and negatively charged with a mean diameter of 182–277 nm. Peptide integrity and stability were maintained after encapsulation and release kinetics followed a sustained profile. We were interested in the relationship between cellular uptake and poly(ethylene glycol) (PEG) in the NP matrix, with results showing enhanced in vitro uptake with increasing PEG content. Peptide-loaded, pegylated (10% PEG)-PLGA NP induced significant cytotoxic and apoptotic effects in MDA-MB-231 breast cancer cells, with no evidence of similar effects in cells pulsed with free peptide. Western blot analysis showed that encapsulated peptide interfered with the proposed signal transduction pathway of the Ran gene. Our novel blockade peptide prevented Ran activation by blockage of regulator of chromosome condensation 1 (RCC1) following peptide release directly in the cytoplasm once endocytosis of the peptide-loaded nanoparticle has occurred. RCC1 blockage was effective only when a nanoparticulate delivery approach was adopted

Evaluation of the Native Killer Yeasts against the Postharvest Phytopathogenic mould of Balady Orange Fruits

Yeasts are some of the most important postharvest biocontrol agents (BCAs). Postharvest oranges frequently deteriorate due to green and blue moulds, leading to significant economic losses. The purposes of the present study were to isolate blue and green moulds from infected orange fruits, to assess the ability of killer yeasts isolated from healthy orange fruits and leaves from orange orchards to control blue and green moulds and to evaluate the additive effect of BCAs in combination with 2% sodium bicarbonate (SBC), 2%, sodium benzoate (SB), 2% calcium chloride, 0.2% salicylic acid (SA) or 0.5% chitosan. Among eight fungi isolated from orange fruits showing symptoms of green and blue mulds infection, two were identified as P. digitatum and P. italicum and selected for in vitro assays. Twenty eight yeast isolates were obtained from orange leaves and from the surface of fruits. All yeasts exhibited high killer activity. Twelve yeasts reduced 22.5 –70% of P. digitatum growth while seven isolates reduced 21.1- 68.5% of P. italicum growth. The most potent yeast isolates were identified as Candida pseudotropicalis, Candida salmanticensis, Candida membranifaciens and Pichia guilliermondii. Combination of the BCAs, C. pseudotropicalis, C. salmanticensis and P. guilliermondii with SBC, CaCl2 or chitosan increased their effectiveness against P. digitatum. While combination of C. pseudotropicalis, C. membranifaciens and P. guilliermondii with these natural compounds decreased their effectiveness against P. italicum. Combination of C. membranifaciens with SA increased its effectiveness against P. digitatum. Sodium benzoate has additive effect on C. pseudotropicalis against P. digitatum and C. pseudotropicalis and P. guilliermondii against P. italicum