An adjuvant effect of Metformin as an anti-fibrotic agent when administered with the anti-schistosomal Praziquantel in Schistosoma mansoni infected mice.

Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.

An adjuvant effect of Metformin as an anti-fibrotic agent when administered with the anti-schistosomal Praziquantel in Schistosoma mansoni infected mice

@#Schistosomiasis is the second most common parasitic disease post Malaria around the world. Praziquantel (PZQ) is known as the most efficient anti- schistosomal drug but has no anti-fibrotic effect. Metformin (Met) is a well-known drug for type 2 diabetes. This study aimed to evaluate the role of Met as anti-schistosomal and anti-fibrotic agents alone or in combination with PZQ treatment. Forty male CD1 mice were divided into four groups (n=10 mice) as following; the first group (Gp1) was served as a negative control. Gp2, Gp3, Gp4, and Gp5 were infected with (60-80) S. mansoni cercariae. After a month of infection, Gp3 was administered orally with PZQ (500 mg/Kg) for 2 consecutive days. Gp4 was administered orally with Met (150 mg/Kg) for 15 consecutive days, and Gp5 was orally administered with PZQ followed by Met for 15 consecutive days at the same doses as in Gp 3 and 4. The results showed that PZQ had potent worms and egg reduction in liver and intestine tissues with no anti-fibrotic effect of the granuloma formation. However, Met or PZQ/Met treatment postinfection led to a reduction in egg count in both liver and intestine tissues with a significant reduction in granuloma site. Treatment of S. mansoni-infected mice with Met or PZQ/Met ameliorated the hematological and biochemical alterations induced by S. mansoni infection. Collectively, Met has no anti-schistosomal activity but led to a reduction in egg deposition and showed an anti-fibrotic effect on granulomatous development either when used alone or in combination with PZQ treatment. This study shed light on the possible role of Met as an anti-fibrotic agent when administered with PZQ for S. mansoni infected humans.

Effect of neodymium: YAG laser posterior capsulotomy on corneal grafts.

Patients undergoing neodymium: yttrium-aluminum-garnet (Nd: YAG) laser posterior capsulotomy for posterior capsular opacification after penetrating keratoplasty were reviewed retrospectively for incidence of graft rejection. All patients underwent extracapsular cataract extraction with posterior chamber intraocular lens implantation (PC-IOL) performed as a separate or combined procedure. Only one of 20 eyes (4.7%) of 20 patients developed corneal graft rejection over a follow-up period of 6 months to 6 years after capsulotomy. Nd: YAG laser capsulotomy does not appear to increase the risk of corneal graft rejection.

New instruments for muscle surgery.

Several techniques have been described and utilized for recession and resection of the extraocular muscles with various technical difficulties and complications. Two new instruments have been designed which may minimize surgical difficulties and provide more accurate and consistent measurements in muscle surgery.

Continuous dosimetry of the biologically harmful UV-radiation in Antarctica with the biofilm technique.

For the first time, a continuous biological dosimetry experiment for cytotoxic solar UV-radiation has been performed in Antarctica. The biologically harmful UV-radiation on the ground was measured at the German Antarctic Georg von Neumayer Station (70 degrees 37' S, 80 degrees 22' W) from December 1990 to March 1992 using the biofilm technique. The UV-sensitive targets were dried spores of Bacillus subtilis which were immobilized on the film surface. The UV-induced inhibition of biological activity, determined photometrically from the protein synthesized after incubation and staining, was taken as a measure for the absorbed UV-dose. Films were exposed in horizontal position for time intervals ranging from 4 days during summer up to 51 and 41 days before and after the polar night respectively. The use of different cut-off filters allowed the calculation of the biologically effective UVA, UVB and the complete UV-radiation (UVA + B). The data were compared with the global radiation and the ozone column thickness indicating an increase of biologically harmful UVB radiation during austral spring at reduced ozone concentrations yielding a radiation amplification factor (RAF) of 1.4, whereas for the total UV(A + B) range the RAF amounted to 0.3.

Long-Term Dosimetry of Solar UV Radiation in Antarctica with Spores of Bacillus subtilis.

The main objective was to assess the influence of the seasonal stratospheric ozone depletion on the UV climate in Antarctica by using a biological test system. This method is based on the UV sensitivity of a DNA repair-deficient strain of Bacillus subtilis (TKJ 6321). In our field experiment, dried layers of B. subtilis spores on quartz discs were exposed in different seasons in an exposure box open to solar radiation at the German Antarctic Georg von Neumayer Station (70 degrees 37'S, 8 degrees 22'W). The UV-induced loss of the colony-forming ability was chosen as the biological end point and taken as a measure for the absorbed biologically harmful UV radiation. Inactivation constants were calculated from the resulting dose-response curves. The results of field experiments performed in different seasons indicate a strongly season-dependent trend of the daily UV-B level. Exposures performed at extremely depleted ozone concentrations (October 1990) gave higher biologically harmful UV-B levels than expected from the calculated season-dependent trend, which was determined at normal ozone values. These values were similar to values which were measured during the Antarctic summer, indicating that the depleted ozone column thickness has an extreme influence on the biologically harmful UV climate on ground.

Haem-apoprotein interactions detected by resonance Raman scattering in Mb- and Hb-derivates lacking the saltbridge His146 beta-Asp94 beta.

The dispersion of the depolarization ratio of oxidation- and spin-marker lines of sperm whale myoglobin derivatives (oxyMb, deoxyMb, ferric Mb-CN) and of ferric Hb-CN have been measured for different pH-values in the acid and alkaline region. No pH-dependence in the region above pH = 6.5 has been found. Below pH = 6.5, however, a significant pH-dependence of the oxyMb-oxidation marker line at 1,375 cm-1 exists. Additionally, a weak pH-dependence of the corresponding 1,355 cm-1 line of the deoxymyoglobin spectrum is observed. This effect can be explained assuming a titration of distal histidine, inducing a rupture of the ligand-imidazole H-bond in the case of oxymyoglobin. The pH-independent depolarization ratio disperson above pH = 6.5 in all systems investigated is explained by the lack of the haemoglobin saltbridge between His(HC3) beta and Asp(FG5) beta, which is essential for the cooperativity in the haemoglobin system.

Metabolism and hepatotoxicity of the naturally occurring benzo[b]pyran precocene I.

The in vitro metabolism of precocene I by liver microsomes from control and treated rats and the effects of precocene I on the function and histology of the rat liver were examined. The major metabolites (80-90% of total metabolites) from all microsomal preparations were the cis and trans 3,4-diols of precocene I produced with a cis/trans isomer ratio of 1:2. These diols appear to arise mainly by spontaneous hydrolysis of precocene I 3,4-oxide. (+)-(3R,4R)-cis- and (-)-(3R,4S)-trans-precocene I 3,4-diols were the predominant enantiomers of the 3,4-diol formed. The enantiomeric excess of these diols (2-50%) is dependent on the microsomal preparation, with microsomes from control rats exhibiting the highest stereoselectivity and microsomes from phenobarbital-treated rats the least. 6-Hydroxyprecocene I was the next major metabolite and was formed to the extent of 5% (control), 10% and 17% (phenobarbital and 3-methylcholanthrene treatment, respectively) of total metabolites. Treatment of rats with a single i.p. dose of precocene I (300 mg/kg) resulted in extensive hepatic damage as evidenced by a marked increase of plasma glutamic pyruvic transaminase levels and histologic observation in liver sections of severe centrolobular necrosis. Although phenobarbital treatment of rats increased the rate of liver microsomal metabolism of precocene I by approximately 50% (nmol products/nmol cytochrome P-450/min) compared to liver microsomes from control rats, hepatic damage caused by precocene I was not significantly affected. Depletion of glutathione levels in the rats with diethyl maleate prior to precocene I treatment dramatically increased the severity of hepatic insult, whereas treatment of the rats with the mixed function oxidase inhibitor piperonyl butoxide prior to treatment with precocene I blocked hepatic damage. Treatment of rats with cysteamine prior to treatment with precocene I protected the animals against the toxic effects. Neither cis nor trans precocene I 3,4-diol nor 3,4-dihydroprecocene I elicited impaired liver function or cellular damage. The above results are consistent with the view that precocene I 3,4-oxide is the metabolite responsible for the hepatotoxic effects observed when precocene I is injected into rats.

Investigation of pH-induced symmetry distortions of the prosthetic group in oxyhaemoglobin by resonance Raman scattering.

The depolarisation ratio and the excitation profiles of some prominent Raman lines of the oxyhaemoglobin spectrum (1,375 cm-1, 1,583 cm-1, 1,638 cm-1) have been measured as functions of the exciting laser frequency. The depolarisation ratio shows a complicated minimum-maximum structure in the preresonant region between Soret- and beta-band of the optical spectrum, which depends on the pH-value of the solution. These dispersion curves are interpreted by fifth-order Loudon theory of the polarizability tensor including static distortions of the haem group, which lower its symmetry from the ideal D4h-symmetry, and enhancement by a second, non-Raman-active phonon. The fitting constants needed to fit the experimental data are related to static distortions of A1g, B1g, B2g, and A2g symmetry types and thus give information on the symmetry lowering from D4h. The variation of the fitting constants with the pH-value of the solution is interpreted to be caused by protonation/deprotonation processes of titrable amino acid groups contributing to the alkaline and acid Bohr effect. The protonation changes the electrostatic interaction energies in the globular protein and destabilizes the salt bridge between His(HC3)beta and Asp(FG1)beta in the R-state. These processes induce distortions of the haem group via haem-apoprotein interactions. Our results give no indication for a dominant role of the covalent Fe2+-N [His(F8)] bond in this process. They are in agreement, however, with the allosteric model of Hopfield, which assumes all interactions to be evenly distributed all over the protein molecule.