Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties.

DNA gyrase and topoisomerase IV show great potential as targets for antibacterial medicines. In recent decades, various categories of small molecule inhibitors have been identified; however, none have been effective in the market. For the first time, we developed a series of disalicylic acid methylene/Schiff bases hybrids (5a-k) to act as antibacterial agents targeting DNA gyrase and topoisomerase IV. The findings indicated that the new targets 5f-k exhibited significant antibacterial activity against Gram-positive and Gram-negative bacteria, with efficacy ranging from 75% to 115% of the standard ciprofloxacin levels. Compound 5h demonstrated the greatest efficacy compared to the other compounds tested, with minimum inhibitory concentration (MIC) values of 0.030, 0.065, and 0.060 µg/mL against S. aureus, E. coli, and P. aeruginosa. 5h had a MIC value of 0.050 µg/mL against B. subtilis, which is five times less potent than ciprofloxacin. The inhibitory efficacy of the most potent antibacterial derivatives 5f, 5h, 5i, and 5k against E. coli DNA gyrase was assessed. The tested compounds demonstrated inhibitory effects on E. coli DNA gyrase, with IC50 values ranging from 92 to 112 nM. These results indicate that 5f, 5h, 5i, and 5k are more effective than the reference novobiocin, which had an IC50 value of 170 nM. Compounds 5f, 5h, 5i, and 5k were subjected to additional assessment against E. coli topoisomerase IV. Compounds 5h and 5i, which have the highest efficacy in inhibiting E. coli gyrase, also demonstrated promising effects on topoisomerase IV. Compounds 5h and 5i exhibit IC50 values of 3.50 µM and 5.80 µM, respectively. These results are much lower and more potent than novobiocin's IC50 value of 11 µM. Docking studies demonstrate the potential of compound 5h as an effective dual inhibitor against E. coli DNA gyrase and topoisomerase IV, with ADMET analysis indicating promising pharmacokinetic profiles for antibacterial drug development.

Impact of hydroxyurea on lymphocyte subsets in children with sickle cell anemia.

BACKGROUND: Hydroxyurea (HU) has beneficial effects in the management of sickle cell anemia (SCA), but there is a paucity of data on the effect of HU on immune cells in SCA. Herein we aimed to evaluate the effect of HU on immune profiles of Egyptian children with SCA. METHODS: This was a controlled prospective cohort study conducted in 30 children with SCA and 30 healthy age-matched controls. Flow cytometry was used to evaluate lymphocyte profiles, including CD8+ T, CD19+ B, CD3+, CD4+, natural killer (NK), NK T, T helper 1 (Th1), Th2, T cytotoxic (Tc1), and Tc2 cells, prior to and after 1 year of treatment with HU. RESULTS: HU treatment led to significant increases in hemoglobin (Hb), red blood cell, and hematocrit counts and a significant decrease in the percentage of sickle Hb, with subsequent improvement in SCA complications. Compared with baseline values, CD3+, CD4+, Th1, and CD8+ T cells were significantly increased, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. CONCLUSIONS: HU has the beneficial effect of restoring the abnormally elevated immune parameters in children with SCA. IMPACT: Hydroxyurea treatment restores the abnormal immune parameters in children with sickle cell anemia. HU treatment led to significantly increased CD3+, CD4+, Th1, and CD8+ T cells, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. Our study showed the impact of HU therapy on immune parameters in children with SCA.

Performance evaluation and life cycle assessment of electrocoagulation process for manganese removal from wastewater using titanium electrodes.

Excess manganese (Mn) concentrations can pose environmental and health risks. Currently, research on Mn removal by electrocoagulation (EC) using transition metal electrodes and the determination of its potential environmental impacts is limited. This study aims to assess the electrocoagulation process's performance with a titanium electrode as a sacrificial anode while also performing a life cycle assessment (LCA) of the process. The initial pH, current density (CD), electrode spacings, electrolyte types, concentrations, and electrode arrangement were all examined. For synthetic wastewater, most of the experiments used a concentration of Mn of 2 mg/L and sodium chloride as a supporting electrolyte at a concentration of 1 g/L. LCA software (OpenLCA 1.11) was used to assess the potential environmental impacts. Optimal operating conditions within the experimental range were as follows: initial pH = 7, CD = 10 mA/cm2, gap distance = 2 cm, and 1 g/L NaCl. Under these conditions, the maximum Mn removal efficiency was 96.5% after 60 min. There was an improvement of 2% rise after 60 min when the temperature increased from 20 °C to 40 °C. For real wastewater, the highest removal efficiencies for Mn and chemical oxygen demand after 60 min were 91.3% and 92%, respectively. The pseudo second order model provides the highest coefficient of determination for expressing the experimental data. Global warming, human non-carcinogenic toxicity, and terrestrial ecotoxicity were the most important categories of impact examined in this work according to the LCA (0.00064 kg CO2 eq, 0.00018 kg 1,4-DCB, and 0.00028 kg 1,4-DCB, respectively). To effectively remove Mn using EC with Ti electrodes, it appears that a period of electrolysis of 10 min would be sufficient under most of the conditions investigated in this study. The reduction in the electrolysis time will lead to a reduction in the operating costs of the system.

Nickel removal from wastewater using electrocoagulation process with zinc electrodes under various operating conditions: performance investigation, mechanism exploration, and cost analysis.

Economically feasible approaches are needed for wastewater treatment. Electrocoagulation (EC) is an electrochemical treatment method that removes various pollutants from wastewater. It has grown in popularity over conventional treatment methods, especially in industrial wastewater, due to its high performance and the ability to remove toxic compounds. However, it is crucial to reduce the costs associated with EC for widespread implementation. It is also important to decrease nickel (Ni) concentrations in wastewater to prevent potential health and environmental problems. Therefore, this study investigates Ni removal from synthetic and real wastewater using electrocoagulation. Zinc, as a novel electrode, was used as the sacrificial anode. Several operating conditions were assessed, including current density, initial pH, electrolysis time, and spacing between electrodes. The maximum Ni removal efficiency, after 90 min, reached 99.9% at a current density of 10 mA/cm2 when the pH was 9.2 and the gap distance was 4 cm. The Ni removal rate reached 94.4% and 94.9% at a 2- and 6-cm spacing, respectively, after 90 min. Anode morphology, kinetic modeling, electrical energy consumption, and cost analysis were also investigated. The type of corrosion was uniform, which is easily predicted compared to pitting corrosion. The comparison between chemical coagulation and electrocoagulation was also reported. Experimental results indicated that the maximum Ni removal rates reached 99.89% after 90 min. The optimum spacing between electrodes was 4 cm, and the optimum current density was 10 mA/cm2. Additionally, the kinetic data were best represented through the second-order Lagergren model. The results demonstrated that the electrocoagulation performance was better than that of chemical coagulation for Ni removal. The maximum electrical energy consumption was 23.79 KWh/m3 for Ni removal.

Efficacy of oral agar in management of indirect hyperbilirubinemia in full-term neonates.

AIM: This prospective randomized case control study aimed to investigate effect of oral agar administration in reducing total serum bilirubin (TSB) levels in full-term neonates with jaundice in comparison with control. MATERIALS AND METHODS: One hundred sixty full-term neonates were enrolled with TSB 10-19 mg/dl at first week of age from Assiut University Children's Hospital. Neonates were divided according to TSB into outpatient group (n = 100) (TSB 10-15 mg/dl) and admitted group (n = 60) (TSB > 15-19 mg/dl). Outpatients group were subdivided into agar group received oral agar and control group received placebo. Admitted group were subdivided into agar group received oral agar plus phototherapy combination and control group received phototherapy alone. Neonates in the agar supplementation received oral agar 600 mg/kg/day dissolved in 10 ml distilled water twice daily till TSB decreased to 7 mg/dl. Daily weight, stool frequency and side effects of treatment were observed for each group. TSB was determined pretreatment then serially every 48 h until TSB level reaching ≤7 mg/dl. RESULTS: Agar fed was effective in lowering TSB in neonates with TSB 10-15 mg/dl. TSB percentage changes were not significantly lower in agar-fed newborn with TSB >15-19 mg/dl compared with control groups after 24 h and 7 days. Age fed shortened the time required to decrease TSB and increased stooling frequency. CONCLUSIONS: Oral agar supplemented feeding at 600 mg/kg/day is safe for full-term neonates and useful in decreasing TSB and phototherapy duration. The efficacy of phototherapy in decreasing TSB level in neonatal hyperbilirubinemia can be augmented with oral agar usage.

In vivo anti-inflammatory and hepatoprotective activities of Orobanche crenata (Forssk.) aerial parts in relation to its phytomolecules.

A total methanolic extract and its sub-extracts of Orobanche crenata (Forssk.) aerial parts were subjected to acute toxicity, anti-inflammatory, and hepatoprotective investigations. The methanolic extract was safe upto 3 g/kg on mice. The EtOAc fraction reduced the carrageenan-induced rat paw edema better than indomethacin. It also demonstrated a drop in the elevated ALT, AST, and TB at 300 mg/kg, better than silymarin. Histopathological examination of liver cells of rats given the EtOAc fraction showed a complete absence of the CCl4-induced cloudy swelling. A phytochemical investigation of the n-hexane and EtOAc fractions yielded 11 compounds [indole-3-carboxylic acid (1), n-butyl palmitate (2), tyrosol (3), L-rhamnonic acid-1,4-lactone (4), ß-sitosterol/stigmasterol mixture (5/5'), ß-sitosterol/stigmasterol glycosides mixture (6/6'), chrysoeriol (7), luteolin (8), apigenin (9), crenatoside (10), and verbascoside (11)] as identified by UV, 1D & 2D NMR and ESIMS techniques. Their reported biological actions were in relation to and supported our herein detected pharmacological findings.

Possible protective and curative effects of selenium nanoparticles on testosterone-induced benign prostatic hyperplasia rat model.

BACKGROUND: Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterised by proliferation of the prostatic epithelium and stroma. Selenium in the form of nanoparticles is an essential metalloid mineral and antioxidant. In this study, selenium nanoparticles (SeNPs) were tested for their potential protective and curative impacts on BPH in rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomised group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNPs before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNPs. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. RESULTS: In the BPH group, serum TE and PSA levels, as well as prostate weight, increased significantly and significant decreases were observed in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly in both the protective and curative groups. There was an increase in proliferating cell nuclear antigen immunoreaction in the BPH group and a decrease in both the protective and curative groups. On transmission electron microscopy of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. CONCLUSIONS: The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.

Bilateral Breast Ochronosis: a Case Report.

Ochronosis is a syndrome characterized by bluish black discoloration due to the deposition of polymerized products of homogentisic acid (HGA) in the connective tissues. The endogenous variety (alkaptonuria), is a rare autosomal recessive metabolic disorder. The disorder is manifested by deficiency of the enzyme homogentisate 1,2-dioxygenase. The characteristic of the condition is a triad of pigmentation of skin, cartilage, and sclera; ochronotic arthropathies and homogentisic aciduria (resulting in darkening of urine). More rarely, it may affect the breast. This rare and interesting case of a woman with ochronosis of both breasts and chest wall, prompted us to write this case report.

Synthesis and antimicrobial evaluation of new nitric oxide-donating fluoroquinolone/oxime hybrids.

A new series of nitric oxide-donating fluoroquinolone/oximes was prepared in this study. The nitric oxide release from the prepared compounds was measured using a modified Griess colorimetric method. The antitubercular evaluation of the synthesized compounds indicated that ketone derivatives 2b and 2e and oximes 3b and 3d exhibited somewhat higher activity than their respective parent fluoroquinolones. Mycobacterial DNA cleavage studies and molecular modeling of Mycobacterium tuberculosis DNA gyrase were pursued to explain the observed bioactivity. More important, antibacterial evaluation showed that oximes 3c-e are highly potent against Klebsiella pneumoniae, with minimum inhibitory concentration (MIC) values of 0.06, 0.08, and 0.034 µM, respectively, whereas ketone 2c and oxime 4c are more active against Staphylococcus aureus than ciprofloxacin (MIC values: 0.7, 0.38, and 1.6 µM, respectively). Notably, the antipseudomonal activities of compounds 2a and 4c were much higher than those of their respective parent fluoroquinolones.

Effect of Hydroxyurea Treatment on the Inflammatory Markers Among Children With Sickle Cell Disease.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential inflammatory marker in sickle cell disease (SCD). This study aimed to evaluate the impact of hydroxyurea (HU) treatment on the value of NLR and some inflammatory mediators in SCD. METHODS: The hematological parameters and clinical events were analyzed in 35 children with SCD under HU treatment and followed up for 1 year and in 20 healthy controls. Enzyme-linked immunosorbent assay was performed for the evaluation of proinflammatory cytokines, including interleukin (IL) 6, IL-8, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α (TNF-α). RESULTS: Hydroxyurea significantly improves most of the hematological parameters in children with SCD. The percentages of hemoglobin fraction S, serum levels of TNF-α and IL-6 were significantly decreased when compared to baseline value but did not reach the value of the healthy control. The HU treatment led to a significant decrease in NLR compared to the baseline values and reached healthy control values. Neutrophil-to-lymphocyte ratio was positively correlated with hs-CRP, TNF-α, and IL-8 serum levels and negatively correlated with percentage of fetal hemoglobin and hematocrit values. The cutoff value of NLR to expect a response to HU among SCD was 3.0, with 76% specificity and 85% sensitivity (area under the curve: 0.85, P < .0001). In conclusion, hydroxyurea induced a decrease in NLR and inflammatory cytokines, which represent a biomarker of inflammation in SCD. The calculation of NLR is a straightforward and cheap method for SCD outcome prediction in young children.

2-Aminothiazole-4-carboxamides Enhance Readthrough of Premature Termination Codons by Aminoglycosides.

Nonsense mutations introduce a premature termination codon (PTC) and are the underlying cause of multiple rare genetic diseases and cancers. Although certain aminoglycosides bind to eukaryotic ribosomes enabling incorporation of an amino acid at the PTC and formation of full-length protein, they are inefficient and toxic at therapeutic doses. Library screening in assays that measure readthrough at a PTC in the TP53 gene in human HDQ-P1 cells identified six novel 2-aminothiazole-4-carboxamide derivatives that potentiate the PTC readthrough (PTCR) efficiency of G418 when used in combination. The two most potent compounds incorporated a 4-indazole motif on the 2-aminothiazole nitrogen and a hydrophobic aryl substituent on the carboxamide nitrogen. These compounds are valuable tools to further investigate the therapeutic potential of aminoglycoside-induced PTCR.

Platelet Activation and Platelet-Leukocyte Aggregates in Type I Diabetes Mellitus.

Hyperglycemia alone may not explain the increased risk of cardiovascular diseases (CVDs) in patients with type 1 diabetes (T1D) compared with type 2. This study emphases on the evaluation of some platelet activity markers in patients with T1D, with relevance to some metabolic disorders as hyperlipidemia and hyperglycemia. This study was performed on 35 patients with T1D and 20 healthy controls. All participants were subjected to full history taking, clinical examination and assay of glycated hemoglobin (HbA1c), and lipid profile. The expression of CD62P and CD36 on platelets and the frequency of platelet-monocyte, and platelet-neutrophil aggregates were assessed by flow cytometry. Patients showed significantly higher expression of CD62P and CD36 than the control group. Platelets aggregates with monocytes were also higher among patients than the control group. Levels of CD36+ platelets, CD62P+ platelets, and platelet-monocyte aggregates revealed significant correlations with the levels of HbA1c, total cholesterol, low-density lipoprotein, and triglycerides. Hyperlipidemia and hyperglycemia accompanying T1D have a stimulatory effect on platelet activation which probably makes those patients vulnerable to CVD than nondiabetics.

Species adulteration in raw milk samples using polymerase chain reaction-restriction fragment length polymorphism.

BACKGROUND AND AIM: Milk adulteration is pivotal because it leads to worse effects in public health as human adverse reactions with clinical signs ranged from gastrointestinal signs to anaphylactic shock. This study was carried out to estimate the prevalence of adulteration in buffalo's milk sold in Assiut City, Egypt. MATERIALS AND METHODS: A total of 50 raw buffalo's milk samples were collected and examined for adulteration by addition of cow's milk. The examination carried out by applying polymerase chain reaction-restriction fragment length polymorphism technique using cytochrome b (cyt b) gene primers and Hinf I enzymes. The size of target gene was 360 bp in both animal species and amplicon can be digested using Hinf I enzyme, this restriction enzyme divided the essential band to clear three bands at 360, 210, and 150 bp in cows' milk, while, the enzyme could not be cleaved the amplicon in buffalo's samples. RESULTS: The obtained results cleared that the incidence of adulteration of buffalo's milk very high percentage reaches 90%. CONCLUSION: It could be concluded that the raw buffalo's milk sold in Assiut City subject to fraudulent practice and thus can lead to public health hazards.

Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation.

Two structurally novel series of histone deacetylase inhibitors (HDACIs) involving two potential surface recognition moieties; 3',4'-dihydro-2'H-spiro[imidazolidine-4,1'-naphthalene]-2,5-dione (in series I) and 1-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide (in series II) were designed, synthesized, and evaluated for their anti-proliferative activities, HDAC inhibitory activities, and their binding modes to HDAC protein. Compounds 5f and 10e showed comparable HDAC inhibitory activity to SAHA. Series II have been also demonstrated as potential HDAC-tubulin dual inhibitors, promoted with structural similarities between (1-(3-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide) nucleus, of series II, and Combretastatin A4. The tubulin inhibitory activities of series II members, together with their docking into colchicine binding site of ß-tubulin were performed. Compound 9a showed remarkable cytotoxicity. Hybrid 10e behaved as potent HDAC-tubulin dual inhibitor. It showed better tubulin inhibition than CA4 as well as its effectiveness against HDAC.

A Parallel Synthesis Approach to the Identification of Novel Diheteroarylamide-Based Compounds Blocking HIV Replication: Potential Inhibitors of HIV-1 Pre-mRNA Alternative Splicing.

A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as active. In subsequent screens, the most potent compound 9 (1C8) was active against wild-type HIV-1IIIB (subtype B, X4-tropic) and HIV-1 97USSN54 (subtype A, R5-tropic) with EC50's of 0.6 and 0.9 µM, respectively. Compound 9 also inhibited HIV strains resistant to drugs targeting HIV reverse transcriptase, protease, integrase, and coreceptor CCR5 with EC50's ranging from 0.9 to 1.5 µM. The CC50 value obtained in a cytotoxicity assay for compound 9 was >100 µM, corresponding to a therapeutic index (CC50/EC50) of approximately 100. Further comparison studies revealed that, whereas the anti-HIV activity for compound 9 and the parent molecule 1 are similar, the cytotoxic effect for compound 9 was, as planned, markedly suppressed.

Protective role of L-carnitine and vitamin E on the testis of atherosclerotic rats.

Atherosclerosis is a condition caused by lipid build-up and inflammation in the arteries, so hyperlipidemia is the major reason for atherosclerosis. Testis was found to be negatively affected by hyperlipidemia which leads to its impaired functions. Vitamin E and l-carnitine have well-known lipid-lowering and antioxidative activities. Triton WR 1339 is a non-ionic detergent, which induces severe hyperlipidemia by inhibition of lipoprotein lipase. The present study evaluates the protective role of vitamin E and l-carnitine on the testis in atherosclerosis and detects the most effective choice for protection against atherosclerosis; vitamin E, l-carnitine or a combination of both. A total of 80 albino male rats were divided into eight groups (10 rats for each group): control (G1), triton (G2), l-carnitine (G3), triton + l-carnitine (G4), vitamin E (G5), triton + vitamin E (G6), l-carnitine + vitamin E (G7) and triton + l-carnitine + vitamin E (G8). Data showed a significant increase in the levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), 17 beta hydroxysteroid dehydrogenase (17 ß HSD), testicular catalase and malondialdehyde (MDA) in G2 when compared with G1, whereas high-density lipoprotein cholesterol (HDL-C), serum testosterone, testicular 17 ketosteroid reductase (17 KSR), total thiol and glutathione-S-transferase (GST) data showed a significant decrease in G2 when compared with G1. Treatment with l-carnitine or/and vitamin E helps in improving the adverse effect of triton; also the histological changes confirm this finding. So the present study recommends all people to include l-carnitine and vitamin E in their diet to be protected against atherosclerosis.

Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: effects of pre- and post-ageing administration.

The ageing process is known to be accompanied by increased oxidative stress and compromised antioxidant defenses. Controlled ozone administration has been shown to be effective in various pathophysiological conditions with an underlying oxidative burden. However, its effect on the biochemical alterations associated with the ageing process has been rarely studied. Therefore, the present work was carried out to study the role of ozone in counteracting the state of oxidative stress associated with ageing in rat liver and kidneys using two experimental models. In the pre-ageing model, ozone was administered prior to the onset of ageing at adulthood and continued after the start of the ageing process (3-month-old rats until the age of 15 months). While in the post-ageing model, ozone was administered after ageing has begun and lasted for one month (14-month-old rats until the age of 15 months). The pre-ageing ozone administration effectively reduced lipid and protein oxidation markers, namely, malondialdehyde and protein carbonyl levels and decreased lipofuscin pigment deposition in rat liver and kidneys. Moreover, it significantly restored hepatic and renal reduced glutathione (GSH) contents and normalized cytosolic hepatic glutathione peroxidase activity. Similar but less pronounced effects were observed in the post-ageing ozone-treated group. Nevertheless, in the latter model ozone administration failed to significantly affect liver and kidney lipofuscin levels, as well as kidney GSH contents. These data provide evidences for potentially positive effects of pre-ageing ozone therapy in neutralizing chronic oxidative stress associated with ageing in rat liver and kidneys.

Serum levels of adrenomedullin and inflammatory cytokines in women with term idiopathic intrauterine growth restriction.

This study aimed to determine the concentrations of adrenomedullin (AM), tumour necrosis factor (TNF)-α and interleukin (IL)-6 in maternal circulation of full-term idiopathic intrauterine growth restriction (IUGR) in relation to appropriate-for-gestational-age (AGA) and the possible correlation of AM to these cytokines. A case-control study included 50 idiopathic IUGR mothers and 25 AGA, who were evaluated regarding their serum levels of AM, TNF-α and IL-6. We found that women with idiopathic IUGR have significantly higher serum levels of AM, TNF-α and IL-6 (p = 0.008; 0.016; 0.029, respectively) and the level of AM was significantly correlated to serum level of TNF-α (r = 0.417, p = 0.003) but not significantly correlated to IL-6 compared with the AGA group. In conclusion, the significant increase of AM, TNF-α and IL-6 in the idiopathic IUGR group might contribute to the uteroplacental haemodynamic alterations and can serve as a useful biochemical marker. Significant correlation between AM and TNF-α could hypothesise the existence of a complex interaction between AM and this inflammatory cytokine.

The effect of monosodium glutamate on the cerebellar cortex of male albino rats and the protective role of vitamin C (histological and immunohistochemical study).

Monosodium glutamate (MSG) is a natural constituent of many foods and was reported to have neurotoxic effects. The aim of this study was to investigate the possible toxic effect of MSG on histological and glial fibrillary acidic protein (GFAP) immunohistochemical features of cerebellar cortex of albino rats and to evaluate the possible protective role of vitamin C against this effect. Thirty rats were divided into 3 equal groups. Group I, control; Group II, treated with 3 g/kg/day of MSG and Group III, received 100 mg/kg/day of vitamin C simultaneously with MSG. After 14 days, cerebellar tissues were obtained and processed to prepare sections stained with H&E, toluidine blue. The GFAP was detected immunohistochemically. Histological examination of group II showed degenerative changes as pyknotic Purkinje and granule cells with areas of degeneration surrounded by inflammatory cells in granular layer. However, group III showed more preserved histological structure of cerebellar cortex. Statistical analysis of area percent of the GFAP immunoreaction among studied groups showed significant increase in group III when compared with group I and group II. However, a non significant increase was detected in group II when compared with group I. In conclusion, MSG has neurotoxic effect leading to degenerative changes in neurons and astrocytes in cerebellar cortex of albino rats and vitamin C supplementation could protect from these changes. Getting more attention to the constituents of food products is recommended and vitamin C could be advised to protect people from food oxidants additives.

Hepatocyte growth factor incorporated into herpes simplex virus vector accelerates facial nerve regeneration after crush injury.

Hepatocyte growth factor (HGF) promotes regeneration of the central nervous system, but its effects on the peripheral nervous system remain unclear. This study was conducted to elucidate the effect of HGF on regeneration of the murine facial nerve after crush injury. To do so, a replication-defective herpes simplex virus vector that incorporated HGF was prepared (HSV-HGF). The main trunk of the facial nerve was compressed by mosquito hemostats, and HSV-HGF, control vector or medium was then applied to the compressed nerve. We found that mice in the HGF group required significantly fewer days for complete recovery from nerve compression. Furthermore, the amplitude of the evoked buccinator muscle compound action potential increased following HSV-HGF application. HGF expression in and around the compressed nerve was demonstrated by enzyme-linked immunoassay and immunohistochemistry. In addition, HSV-HGF introduction around the damaged nerve significantly accelerated recovery of function of the facial nerve. These data suggest a possible role of HGF in promoting facial nerve regeneration after nerve damage. Furthermore, this viral delivery method may be applied clinically for many types of severe facial palsy during facial nerve decompression surgery.