Spontaneous clearance of chronic hepatitis C infection is associated with an internal ribosomal entry site IIId stem loop structure variant.

Aim: To investigate if any mutations in hepatitis C virus (HCV) internal ribosome entry site (IRES) can inhibit the translation of viral polyprotein. Materials and Methods: A 26-year-old male patient infected with HCV 10 years ago was followed up. After 9 years of chronic infection. The patient had managed to resolve the infection for a period of 9 months, after which the patient experienced a viral recurrence characterized by high viral load and diverse HCV quasispecies. The IRES structures of the viral strains that disappeared were comparable with those that are currently active using structural mutational analysis. Results: A novo mutational position 254 combined with a rarely observed mutation at position 253 in the stem of the IIId subdomain were observed and the new conformation had an octa-apical loop (AGUGUUGG) and a shift in the 3 ` GU from the loop to the stem. Conclusions: These mutations were found to be highly deleterious, and they affected the direct binding of the IIId loop to the 40S ribosomal subunit with a subsequent inhibition of translation of viral polyprotein and clearance of the virus.

Rheological studies on different oily vehicles for pharmaceutical preparations

The rheological properties of oily vehicles based on patents of non-aqueous vehicles for pharmaceutical suspensions were studied. The effects of different concentrations of suspending agents and different excipients on the flow curves were also investigated. A Rotovisko viscometer [Haake] fitted with concentric cylinder sensors, NV measuring head- 500 and a temperature controlled water jacket at 37°C was used. The results showed that Fractionated Coconut Oil [FCO] alone and with 0.7% w/v lecithin exhibited Newtonian behavior. Dispersions of aluminium stearate, hydrogenated castor oil, Cab-o-sil and sucrose in FCO exhibited pseudoplastic behavior. Aluminium stearate 1% w/v and above and the oily vehicle containing aluminium stearate, hydrogenated castor oil, lecithin and sucrose exhibited thixotropic pseudoplastic properties. The omission of lecithin from the later vehicle resulted in a decrease in the apparent viscosity and the loss of thixotropy. The thixotropic pseudoplastic behavior of oily vehicles is a desirable property in liquid pharmaceutical systems that ideally should have a high consistency in the container, yet pour or spread easily after they had been stirred vigorously. Possible reasoning and suggestions were discussed

Detection of serum prostate specific antigen in lactating, pregnant, and advanced breast cancer Sudanese Women

Introduction: Although prostate-specific antigen (PSA) is the most valuable tumor marker for the diagnosis and management of prostate carcinoma; it is widely accepted that PSA is not prostate specific. Objectives: The aim of this study is to address the possibility of using the PSA as marker for the sex assignment in different categories and relevance of this test in women problems. Method: We have evaluated the measurement of serum total PSA for differentiation between Sudanese women with advanced breast cancer (n= 10); and those are lactating (n=10); pregnant (n=10) compared with 20 healthy women as control group. Serum total PSA (TPSA) was measured using immuno-radiometric assay (IRMA). Results: In this study the mean age was significantly higher advanced breast cancer groups compared with lactating group (P0.01). The mean serum PSA levels in the healthy control women examined (nsignificant high level of total PSA in serum of advanced breast cancer compared with the normal group (P 0.05). Conclusion: These results indicated the possible use of total PSA to distinguish between healthy women and/or women with advanced breast cancer

Urological Injuries during Pelvic Surgery in Women; Gezira; Central Sudan

Injuries to the ureter and bladder are common in female pelvic surgery; sometimes extremely common to be considered as traditional. This is a retrospective study conducted in Gezira Hospital for Renal Disease and Surgery; Medani Teaching Hospital and Medani Maternity Hospital; #ad Medani; Sudan. #e included $paetents 'ith urological injuries follo'ing obstetrical gynecology interveneton in the previous ( years. The interaoperaetve injuries consettuted; -.; 'hile the remote injuries 'ere 6+7(.6 -.. #e conclude that the urological injuries are common complications during pelvic surgery; associated mainly 'ith abdominal hysterectomies and Cesarean section

Effects of pharmaceutical excipients on the in vitro release rate of sodium salicylate from oily vehicles

The work objective was to study the possible effects of different pharmaceutical excipients on the release of sodium salicylate from oily vehicles. Several formulations of Fractionated Coconut Oil [FCO] containing different pharmaceutical additives were prepared. The release rate behaviour of sodium salicylate from these oily formulations was investigated using a dialysis method. The time required for 30% and 50% of the salicylate to appear in solution outside the dialysis sac [t[30%] and t[50%]] respectively, were used as indices for estimating the release rate. The results of this study showed that the aluminium stearate retards the release rate of salicylate specially when its concentration is 1.5%w/v or more. Oily formulation containing 0.5% w/v aluminium stearate +0.7%w/v lecithin +0.35% w/v hydrogenated castor oil +20% w/v sucrose in FCO and oily formulation containing 0.5% w/v Cab-o-sil + 20%w/v sucrose in FCO delayed the release rate of the drug. However, the inclusion of sucrose in the formulations complicates the situation and enhances the release rate especially at the later stages. The enhancing effect of sucrose on the release rate is nullified by the inclusion of 1% w/v Cab-o-sil. Possible reasons for these effects are discussed with particular reference to the tendency forming globules of sucrose, due to the osmotic effect inside the dialysis sac. Oily formulations [0.5% w/v aluminium stearate + 0.7%w/v lecithin + 0.35% w/v hydrogenated castor oil + 20% w/v sucrose in FCO] and [0.5% w/v Cab-o-sil + 20%w/v sucrose in FCO] can be used as a depot preparations for chronic disease conditions. The enhancing effect of sucrose on the release rate of salicylate can be beneficial if acute response is required. Extrapolation of this study on tablets, capsules and i.m. injection formulations is suggested

Biochemical and morphological analysis of cell death induced by Egyptian cobra (Naja haje) venom on cultured cells

We investigated the in vitro process of cell death caused by Egyptian cobra venom on primary human embryonic kidney (293T) and mouse myoblast (C2C12) cell lines. The aim of these studies was to provide further information about triggering cell death, and suggest methods for eliminating unwanted cells, such as tumour cells. Both cell lines were treated with 10, 20, and 50 m g/ml of Egyptian cobra (Naja haje) venom in serum free media (SFM) and incubated for 8 hours. Total activities of the lactate dehydrogenase (LDH) and creatine kinase (CK) released in the culture during venom incubation were used as an indicator of the venom in vitro cytotoxicity. Cell injury was morphologically recognized and apoptosis determined by a Fluorescing Apoptosis Detection System and confirmed by staining nuclear DNA with DAPI. Our data clearly demonstrated marked cytotoxic effects and acute cell injury for both cell lines. Release of LDH and CK into the culture media induced by the venom correlates well with the morphological changes and extent of cell death. Mostly, these consequences were time and dose-dependent in both cell lines. The results obtained from this study indicated that cobra venom cause cell death by two different mechanisms: necrosis and induction of apoptosis. The apoptotic mechanism, accompanied by cell necrosis, mediated cell destruction of both tested cell lines; however, necrosis was predominant in the C2C12 cell line while apoptosis, in 293T cells. This unusual form of cell death induced by cobra venom may represent a combination of apoptosis and necrosis within the same cell. This is a first-hand investigation showing the apoptotic effects of N. haje venom at the cellular level. However, the contribution of the apoptotic pathway may be dependent on concentration and/or time of exposure to snake venom.(AU)

Effect of gastrointestinal transit on the bioavailability of orally administered drugs in rabbit

The effect of gastrointestinal [GI] transit rate on the absorption behavior of orally administered drug was investigated, using aqueous, oily and aqueous vehicles pretreated with propantheline, in rabbits and three-way crossover design. The absorption behavior was examined for sodium salicylate as a model drug since it is well absorbed from both the stomach and small intestine. The three bioavailability parameters, Tmax, Cmax and AUCO-24, that were obtained from the three different treatments, were compared. The results clarified that delay in the gastric emptying rate [GER], brought about by the oil or by propantheline, lowers the rate of absorption and enhances the extent of absorption of salicylates compared with the aqueous solution. The viscosity of the oil plays no significant role in the results obtained

Cytotoxic and apoptotic effects of scorpion Leiurus quinquestriatus venom on 293T and C2C12 eukaryotic cell lines

Scorpion venom toxicity is of major concern due to its influence on human activities and public health. The cytotoxicity and apoptosis induced by scorpion L. quinquestriatus venom on two established eukaryotic cell lines (293T and C2C12) were analyzed. Both cultured cell lines were incubated with varying doses (10, 20, and 50 µg/ml) of scorpion venom in serum free medium (SFM) for 0.5, 1, 2, 4, and 8 hours at 37°C. The percentage of total lactate dehydrogenase (LDH) released in the culture during venom incubation was used as an index of cell damage. Control culture was treated with an equal amount of SFM. Cell injury was recognized morphologically and apoptosis was researched by a Fluorescing Apoptosis Detection System using the principle of TUNEL (TdT-mediated dUTP Nick-End Labelling) assay and confirmed by another assay concerning nuclear DNA staining with DAPI stain. Cytotoxicity was remarkable and cell survival highly reduced at the highest tested concentration (50 µg/ml). These effects were rapid and observed within 30 minutes. The apparent initial damage to the nucleus and lysis of the plasmalemma and/or organelle membranes, which was evident by a significant increase in cytosolic LDH release, suggested that this toxin acts at the membrane level. The morphological changes that occurred in apoptotic cells include condensation and compartmentalization of nuclear and cytoplasmic materials into structurally preserved membrane-bound fragments or blebs. The cytotoxic effects are dose and time dependent and cell death by apoptosis was more characteristic of 293T cells than C2C12 cells. The apoptotic effects were more prominent and clear in the early stages of toxicity, while other forms of cell damage such as swelling, rupture, and/or necrosis occurred at later stages.