Evaluation of the teratogenic potency of bulk zinc oxide and its nanoparticles on embryos of the freshwater snail, Helisoma duryi.

Bulk zinc oxide (ZnO-BPs) and its nanoparticles (ZnO-NPs) are frequently used in various products for humans. Helisoma duryi embryos can serve as effective model organisms for studying the toxicity of NPs. This study aimed to compare the teratogenic potency of ZnO-BPs and ZnO NPs in the embryonic stages of H. duryi to evaluate the utility of this snail as a bioindicator for ZnO-NPs in the aquatic environment. The mechanisms of teratogenesis were evaluated by determination of the LC50, studying the effect of sub-lethal concentrations of both ZnO forms on the embryos, and studying their enzyme activity, oxidative stress, and biochemical analysis. The SDS-PAGE electrophoresis was undertaken to assess the effect of ZnO-BPs and ZnO NPs on protein synthesis. The results revealed that the veliger stage of H. duryi is the specific stage for bulk and nano ZnO. ZnO-NPs proved to be more toxic to snails' embryos than ZnO-BPs. Exposure to ZnO influences specific types of defects in development, which in the case of BPs are far less drastic than those caused by NPs. Thus, the toxicity of ZnO-NPs in embryonic development is due to their unique physicochemical properties. The observed malformations include mainly hydropic malformation, exogastrulation, monophthalmia, shell misshapen, and cell lyses. Almost all tested oxidative biomarkers significantly changed, revealing that ZnONPs display more oxidative stress than ZnO-BPs. Also, the low concentration of ZnO induces many disturbances in the organic substances of veliger larvae, such as a decrease in the total protein and total lipid levels and an increase in the glycogen level. The results indicated that ZnO-BPs increase the number of protein bands. Conversely, ZnO-NPs concealed one band from treated egg masses, which was found in the control group. Embryos of snail are an appropriate model to control freshwater snails. This study demonstrates that H. duryi embryos can serve as effective model organisms to study the toxicity of ZnO-NPs.

Reproductive performance of freshwater snail, Helisoma duryi under the effect of bulk and nano zinc oxide.

Nanotechnology has been used to apply nanoparticle essential elements to enhance the ability of animals to absorb these elements and consequently improve their reproductive performance. High concentrations of nanoparticles (NPs) can directly harm a range of aquatic life forms, ultimately contributing to a decline in biodiversity. Helisoma duryi snails are a good model for studying the toxicological effects of bulk zinc oxide (ZnO-BPs) and nano zinc oxide (ZnO-NPs) on freshwater gastropods. This study aimed to compare the toxic effects of ZnO-BPs and ZnO-NPs on H. duryi snails and explore how waterborne and dietary exposure influenced the reproductive performance of this snail. ZnO-BPs and ZnO-NPs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray powder (XRD). This study revealed that the size of ZnO-BPs and ZnO-NPs were 154 nm and 11-31 nm, respectively. The results showed that exposure of adult snails to sub-lethal concentrations of both ZnO forms (bulk and nano) for 24 h/week for 4 weeks markedly changed their reproductive performance in a concentration-dependent manner, where fecundity was negatively affected by high concentrations. It was concluded that dietary exposure to the lowest tested concentration of ZnO-NPs (1 ppm) has a positive effect as the number of eggs and egg masses/snails increased and the incubation period decreased. Also, poly-vitelline eggs (The formation of twins) were observed. ZnO-NPs at low concentrations positively affect the reproductive performance of snails, especially after dietary exposure. The results revealed that 1 ppm ZnO-NPs could be supplementary provided to snails to improve their fertility, reduce the developmental time course, increase hatchability percentage, and produce poly-vitelline eggs.

Punicalagin's Protective Effects on Parkinson's Progression in Socially Isolated and Socialized Rats: Insights into Multifaceted Pathway.

Parkinson's disease (PD) is a gradual deterioration of dopaminergic neurons, leading to motor impairments. Social isolation (SI), a recognized stressor, has recently gained attention as a potential influencing factor in the progress of neurodegenerative illnesses. We aimed to investigate the intricate relationship between SI and PD progression, both independently and in the presence of manganese chloride (MnCl2), while evaluating the punicalagin (PUN) therapeutic effects, a natural compound established for its cytoprotective, anti-inflammatory, and anti-apoptotic activities. In this five-week experiment, seven groups of male albino rats were organized: G1 (normal control), G2 (SI), G3 (MnCl2), G4 (SI + MnCl2), G5 (SI + PUN), G6 (MnCl2 + PUN), and G7 (SI + PUN + MnCl2). The results revealed significant changes in behavior, biochemistry, and histopathology in rats exposed to SI and/or MnCl2, with the most pronounced effects detected in the SI rats concurrently exposed to MnCl2. These effects were associated with augmented oxidative stress biomarkers and reduced antioxidant activity of the Nrf2/HO-1 pathway. Additionally, inflammatory pathways (HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1 and JAK-2/STAT-3) were upregulated, while dysregulation of signaling pathways (PI3K/AKT/GSK-3ß/CREB), sustained endoplasmic reticulum stress by activation PERK/CHOP/Bcl-2, and impaired autophagy (AMPK/SIRT-1/Beclin-1 axis) were observed. Apoptosis induction and a decrease in monoamine levels were also noted. Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl2. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN's mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3ß/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2.

Neuroprotective Effects of Phytochemicals against Aluminum Chloride-Induced Alzheimer's Disease through ApoE4/LRP1, Wnt3/ß-Catenin/GSK3ß, and TLR4/NLRP3 Pathways with Physical and Mental Activities in a Rat Model.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with abnormal cognition. AD is aided in its initiation and progression by hereditary and environmental factors. Aluminum (Al) is a neurotoxic agent that causes oxidative stress, which is linked to AD progression. Additionally, Nrf2/HO-1, APOE4/LRP1, Wnt3/ß-catenin, and TLR4/NLRP3 are the main signaling pathways involved in AD pathogenesis. Several phytochemicals are promising options in delaying AD evolution. OBJECTIVES: This study aimed at studying the neuroprotective effects of some phytochemicals as morin (MOR), thymol (TML), and thymoquinone (TMQ) on physical and mental activities (PhM) in Al chloride (AlCl3)-induced AD rat model. Another objective was to determine the specificity of phytochemicals to AD signaling pathways using molecular docking. METHODS: Eighty male Dawley rats were divided into eight groups. Each group received: saline (control group), AlCl3, (ALAD), PhM, either alone or with a combination of MOR, TML, and/or TMQ for five weeks. Animals were then subjected to behavioral evaluation. Brain tissues were used for histopathological and biochemical analyses to determine the extent of neurodegeneration. The effect of phytochemicals on AlCl3-induced oxidative stress and the main signaling pathways involved in AD progression were also investigated. RESULTS: AlCl3 caused a decline in spatial learning and memory, as well as histopathological changes in the brains of rats. Phytochemicals combined with PhM restored antioxidant activities, increased HO-1 and Nrf2 levels, blocked inflammasome activation, apoptosis, TLR4 expression, amyloide-ß generation, and tau hyperphophorylation. They also brought ApoE4 and LRP1 levels back to normal and regulated Wnt3/ß-catenin/GSK3ß signaling pathway. CONCLUSIONS: The use of phytochemicals with PhM is a promising strategy for reducing AD by modulating Nrf2/HO-1, TLR4/NLRP3, APOE4/LRP1, and Wnt3/ß-catenin/GSK-3ß signaling pathways.

Neuroprotective Effect of Morin Hydrate against Attention-Deficit/Hyperactivity Disorder (ADHD) Induced by MSG and/or Protein Malnutrition in Rat Pups: Effect on Oxidative/Monoamines/Inflammatory Balance and Apoptosis.

Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)-a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals' behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1ß), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.

Design and synthesis of chromone-based monoamine oxidase B inhibitors with improved drug-like properties.

The absence of disease modifying drugs in Parkinson's disease therapy urges for new chemical entities acting on relevant PD-associated biological targets. As a result, developing selective and reversible inhibitors targeting MAO-B is still a desirable line of therapeutic research. Within this framework, a small library of chromone derivatives was synthesized and screened towards human monoamine oxidases. Structural modifications on the chromone 3-phenylcarboxamide resulted in potent MAO-B inhibitors with an improved drug-like profile, and for the first time we obtained potent and selective chromone 2-phenylcarboxamides acting in the low nanomolar range. Compounds 5-hydroxy-4-oxo-N-phenyl-4H-chromene-3-carboxamide (38) (IC50 = 13.0 nM) and N-(4-chlorophenyl)-5-hydroxy-4-oxo-4H-chromene-3-carboxamide (41) (IC50 = 8.3 nM) stood out as reversible, potent, selective and non-cytotoxic MAO-B inhibitors bearing a favourable drug-like profile. Both compounds displayed cytoprotective effects towards iron(III) oxidative stressor.

Effect of Oral Methyl Prednisolone on Different Radiological Patterns of Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an immune-mediated disorder that causes inflammation of interstitial lung, bronchioles, and alveoli. Although corticosteroids have been used as first line treatment for HP for many years, it does not provide satisfactory results in all patients. The aim of this study is to compare the effect of oral methylprednisolone on different radiological patterns of HP to identify the most adequate candidates for corticosteroids. PATIENTS AND METHODS: Fifty-three patients with confirmed diagnosis of HP were divided into two groups according to their radiological patterns based on high resolution computed tomography (HRCT) findings. The first group included 21 patients with fibrotic HP (fHP), the second group included 32 patients without fibrosis; non-fibrotic HP patients (nfHP). The second group is divided into 3 subgroups: mosaic, attenuation, centrilobular nodules and finally, ground-glass opacities. All patients were administered methylprednisolone by dose 0.5mg/kg/day for eight consecutive weeks. HRCT was performed at the beginning of the study. Spirometry, six-minute walk and oximetry were performed periodically to assess the patients' progress. RESULTS: Upon finalizing the treatment process, a significant improvement was noticed in FEV1 (p < 0.001), FVC (p <0.001), six-minute walk test (p =0.001) and oximetry (p <0.05) in nfHP compared to the fHP patients. However, there was a significant improvement in (p <0.01), FVC (p <0.01), oximetry (p <0.01) and six-minute walk test (p <0.01) in fibrotic patients after receiving the treatment. There was no significant difference in the response of FEV1 (p =0.82), FVC (p =0.15), six-minute walk test (p =0.36) and oximetry (p =0.27) among the subgroups of nfHP patients. CONCLUSION: It was accordingly concluded that corticosteroid treatment is more effective in treatment of nfHP than fHP patients but still has effect on fibrotic patients. There is no significant difference in the response to corticosteroids among nfHP patients' subgroups.

Unique localization of disseminated pancreas in the oesophagus of catfish (clarias gariepinus) with reference to sexual dimorphism.

BACKGROUND: The fish pancreas has been reported to be composed of two portions: compact and disseminated. However, little has been elucidated in catfish. The present study describes a unique localization of the disseminated pancreas in African catfish. METHODS: The sections were obtained and used for either routine histological examination following staining with haematoxylin and eosin (H & E), periodic acid-Schiff's, or were subjected to immunohistochemical staining for detection of both insulin-producing ß cells and glucagon-producing alpha cells. RESULTS: Our investigation showed that the pancreas of catfish consisted of both compact and disseminated portions. The compact pancreas was embedded in the mesenteric adipose tissue between the spleen, stomach and liver. However, the disseminated one showed unique localization in the tunica adventitia of the middle portion of the oesophagus. The pancreas consisted of two portions, exocrine and endocrine. Furthermore, in both types of pancreas, the female showed a significantly higher ratio for the endocrine islet area/pancreatic tissue area than that of the male and also a significantly higher ratio for both insulin- and glucagon-positive area/islet area in the female pancreas (compact and disseminated) than that of the male. IN CONCLUSION: The present study provides evidence on a unique localization of the disseminated pancreas in the oesophagus of catfish. Furthermore, we revealed sex-related difference in the endocrine portion in both pancreatic tissues with more development in the female. The study suggests that sex hormones could be contributed to such sexual dimorphism. However, further investigation is required to compare the degree of development during the spawning and resting seasons.

Protective effect of Spirulina platensis against physiological, ultrastructural and cell proliferation damage induced by furan in kidney and liver of rat.

The modulatory role of the Spirulina platensis (SP) against furan-induced (FU) hepatic and renal damage was assessed in this study. For achieving this, sixty rats were distributed into six groups: control group, SP-administered group (300 mg/kg b.wt orally for 28 days), a FU-intoxicated group (16 mg/kg b.wt, orally, daily for 28 days), protective co-treated group SP/F (administered SP 300 mg/kg b.wt, one week before, and concurrently with FU intoxication), therapeutic co-treated group FU/SP (administered SP 300 mg/kg b.wt, one week after FU intoxication for 28 days) and protective/therapeutic co-treated group SP/FU/SP (administered SP one week before and after, concurrently with FU intoxication). Subsequently, the biochemical responses and the histology of hepatic and renal tissues in treated rats were assessed. The results indicated that FU intoxication induced a significant hepato- and nephropathy represented by the elevation in the values of tissue injury biomarkers and reduction in protein levels. Histologically, a wide range of morphological, cytotoxic, inflammatory, and vascular alterations as well as downregulation in the immunoexpression of the proliferating cell nuclear antigen (PCNA) and the proliferation-associated nuclear antigen (Ki-67) were induced by FU intoxication. Oral SP administration, particularly in the protective/therapeutic co-treated group, markedly supressed the serum levels of the tissue injury biomarkers, diminished the inflammatory response, restored the cytotoxic alterations, upregulated the immunoexpression of PCNA and Ki-67, and restored the perturbed morphology of the hepatic and renal tissues. In conclusion, the obtained data demonstrated that SP co-administration elicits both protective and therapeutic potential against the FU-induced hepato- and nephropathy.

Ultrastructural studies on the pancreatic acini in duck (Anas boscas) and pigeon (Columba livia).

The aim of this research work was to study the histological structure of the pancreatic acini by transmission electron microscope in two avian species, duck and pigeon. The specimens were collected and processed for electron microscopic study. The results showed that the acini of the two avian species were two types; the first one was an electron dense and the second one an electron lucent. The light acinar cells were larger in size than the dark cells. These cells contained centrally located ovoid nuclei with prominent nucleoli and abundant euchromatin. The cytoplasm was electron lucent, with many rough endoplasmic reticulum, polymorphic mitochondria. Numerous zymogen granules were distributed in the basal part and around the nucleus, so these cells considered active cells. The dark acinar cells were characterized by an electron dense cytoplasm. The most prominent cell organelle in these cells were the zymogen granules that appeared in different sizes while other organelles as mitochondria, and rough endoplasmic reticulum were inconspicuous or few, so these cells were considered as inactive cells. The nucleus with indented nuclear membrane located centrally with prominent nucleoli and abundant heterochromatin. Prominent intercellular spaces between the individual acinar cells, as well as well-developed basement membrane separating the electron dense cells and the lumen contained the secretion between acinar cells. It could be concluded that the acinar cells in ducks and pigeons were divided into two types, that is, light and dark acinar cells which mainly attributed to the activity of these cells.

Histological and ultrastructural studies on the coronary artery of adult domestic dog (Canis familiaris).

The objective of this work was to study the histological structure of the dog's coronary artery by light and transmission electron microscope (TEM). The coronary artery consisted of three tunics: tunica intima, tunica media and tunica adventitia. The tunica intima consisted of endothelium rested directly on internal elastic lamina without the subendothelial connective tissue layer. The tunica media were composed of smooth muscle fibres interspersed with few elastic and collagen fibres. The tunica adventitia consisted of collagen and elastic fibres intermingled with fibroblast cells; it had vasa vasorum and nervi vasorum. Some histomorphometric measurements were performed and compared statistically. The ultrastructural study showed that the endothelial cells were communicated through complex junctions and characterised by filiform cytoplasmic processes passed through the opening of the underlying internal elastic membrane. The smooth muscle fibres of tunica media communicated with each other through cytoplasmic processes. The tunica adventitia showed minute non-myelinated nerve. This work revealed that the dog's coronary arteries are typical muscular arteries, which show little structural variations from that of other mammals.

Enhancement of zaleplon oral bioavailability using optimized self-nano emulsifying drug delivery systems and its effect on sleep quality among a sample of psychiatric patients.

The aim of this work is to develop self-nano emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of zaleplon (Zal) as a poorly water-soluble drug. Moreover, the bioavailability and the effect on the quality of sleep among a sample of psychiatric patients is to be assessed. D-optimal mixture design was used for optimization. Optimized SNEDDS formulation was evaluated for droplet size, transmission electron microscope (TEM) and in-vitro dissolution test. Zal bioavailability was evaluated by determining its serum concentration and pharmacokinetic parameters in 8 patients after oral administration. Effect on sleep quality was assessed among 40 psychiatric patients. Patients' sleep quality was assessed in 40 psychiatric patients before and after medication using the Arabic version of the Pittsburgh Sleep Quality Index (PSQI). Zal- SNEDDS appeared as nano-sized spherical vesicles. Moreover, Zal was completely dissolved from optimized formulation after 45 min indicating improved dissolution rate. Zal-SNEDDS showed significantly higher Cmax, Tmax and AUC0→∞ compared to commercial product after oral administration. Zal-SNEDDS significantly improved the total score of PSQIs (p < .001) with higher subjective sleep quality, reduced sleep latency, improved day time function and sleep disturbance (p < .001). Using sleep medication was reduced significantly (p = .027). However, it did not modify sleep duration or sleep efficiency. SNEDDS have improved Zal solubility and enhanced its bioavailability. Furthermore, Zal-SNEDDS have improved the total score of PSQIs and may be considered a good choice to enhance the quality of sleep among psychiatric patients.

A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major.

BACKGROUND: Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. OBJECTIVES: This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. METHODS: A single, randomized, placebo-controlled trial was performed in 40 ß-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5-5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. RESULTS: After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight (p<0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms (p<0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. CONCLUSION: The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.

Effective method of evaluating myocardial iron concentration in pediatric patients with thalassemia major.

BACKGROUND: The use of T2* magnetic resonance imaging (MRI) has been promoted by recent studies as a noninvasive method for the detection of iron overload in thalassemia major patients. This study aims to estimate the iron load in the heart and liver of thalassemia major patients using T2* MRI and to determine its correlation with the left ventricle ejection fraction and serum ferritin level. METHODS: Forty ß-Thalassemia major patients were included in the study. We evaluated the serum ferritin level, echocardiography, cardiac T2*, myocardial iron concentration (MIC), liver iron concentration (LIC) and hepatic T2* in all patients. CMR T2* findings were categorized as normal cardiac T2* (T2* >20 ms) or abnormal cardiac T2* (T2* <20 ms). RESULTS: The study found that 85% of patients had a normal cardiac T2* value. The median serum ferritin level was 2189. A significant inverse correlation was found between the serum ferritin level and the cardiac T2* (r=-0.381, =0.015); however, the correlations between serum ferritin and the hepatic T2* and liver iron concentration were statistically non-significant (P=0.539 and P=0.637, respectively). Additionally, the LVEF correlation was statistically non-significant with SF, hepatic T2* and cardiac T2*. CONCLUSION: Regardless of the serum ferritin level or left ventricle function, a cardiac T2* MRI should be done for all patients with ß-Thalassemia major in order to estimate the myocardial iron concentration.

Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study.

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan® 1% cream. Follow up was done for 4 weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between -21 and -33 mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p < .05) in therapeutic response (1.4-fold; healing%, 4-fold; complete eradication) in terms of clinical cure and mycological cure rate from PV against marketed cream. Findings of the study suggest that the developed FLZ loaded SLNs topical gels have superior significant fast therapeutic index in treatment of PV over commercially available Candistan® cream.

Autologous transplantation of CD34(+) bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia.

Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia.

The role of hepatic expression of STAT1, SOCS3 and PIAS1 in the response of chronic hepatitis C patients to therapy.

BACKGROUND: The underlying mechanisms of hepatitis C virus (HCV) resistance to treatment are unknown. Signal transducers and activators of transcription (STAT) proteins play a critical role in antiviral defense. OBJECTIVE: To explore some of the mechanisms of HCV resistance to interferon, the expression of STAT1 and its negative regulators, protein inhibitor of activated STAT (PIAS1) and suppressor of cytokine signalling (SOCS3), in liver tissues of both inteferon responders and nonresponders in chronic HCV patients. METHODS: Sixty patients were divided into the following groups: group 1a comprised 38 treatment-responder chronic HCV patients; group 1b consisted of 22 treatment-nonresponder chronic HCV patients; and group 2 consisted of six control subjects. Liver biopsies were examined for histological scoring; STAT1, SOCS3 and PIAS1 expression was analyzed using Western blotting methods. RESULTS: STAT1 expression in the liver tissue of patients in group 1 was significantly increased compared with group 2 patients (P=0.001), while no significant difference in expression was observed between group 1a and group 1b patients (P=0.747). However, phosphorylated STAT1 protein was expressed at a significantly higher level in liver tissue of patients in group 1a compared with patients in group 1b (P=0.001). Western blot analysis of PIAS1 and SOCS3 protein expression in liver tissues from groups 1 and 2 revealed significantly increased expression in group 1 compared with group 2 (P=0.001). In addition, PIAS1 and SOCS3 protein expression was significantly higher in the liver tissues of patients in group 1b compared with patients in group 1a. CONCLUSION: Levels of STAT1 and/or the protein expression of its negative regulators, PIAS1 and SOCS3, may be a good predictor of response to therapy. These could be used as biomarkers that are easily detected by Western blotting or immunostaining during standard histopathological liver biopsy analysis.