Memantine versus Ginkgo biloba Extract: A Comparative Study on Cognitive Dysfunction Treatment in a Novel Rat Model.

Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimer's disease, the most prevalent type of dementia. Currently, no effective medications are available to stop or reverse Alzheimer's disease. Ginkgo biloba extract, commonly referred to as EGb 761, is a natural product made from the leaves of the G. biloba tree. It has long been demonstrated to have therapeutic benefits in Alzheimer's disease. The current study assessed the beneficial effects of EGb 761 against Alzheimer's disease in comparison with memantine, a standard treatment for Alzheimer's disease. The scopolamine-heavy metals mixture rat Alzheimer's disease model is a newly created model to study the effects of EGb 761 oral therapy on cognitive performance and other Alzheimer's disease-like changes over a 28-day experimental period. This new Alzheimer's disease model provides better criteria for Alzheimer's disease hallmarks than the conventional scopolamine model. The EGb 761 reversed memory and learning deficits induced by the scopolamine-heavy metals mixture. These outcomes were linked to a more pronounced inhibitory effect on acetylcholinesterase, caspase-3, hippocampal amyloid-beta protein (Aß1 - 42), phosphorylated tau protein counts, and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) compared to the memantine-treated group. Furthermore, EGb 761 treatment considerably reduced lipid peroxidation (malondialdehyde) and improved reduced glutathione levels compared to memantine. Our results suggest EGb 761's potential in treating central nervous system disorders. It's a promising candidate for future Alzheimer's disease therapeutic exploration. This study also highlights the need for future research to focus on the positive benefits of herbal medicines.

Possible Role of Netrin-1/Deleted in Colorectal Cancer/Vascular Endothelial Growth Factor Signaling Pathway in the Pathogenesis of Placenta Accreta Spectrum: A Case-control Study.

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

Hypoxia-inducible Factor-1α and mTOR as a Potential Therapeutic Target in Endometriosis: An Immunohistochemical Study.

BACKGROUND AND STUDY AIM: We aim to study the immunohistochemical expression of both hypoxia-inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) in endometriosis to provide new evidence for a targeted endometriosis therapy. PATIENTS AND METHODS: This study comprised 106 endometriotic cases diagnosed clinically and histopathologically. The immunohistochemical method was done to determine the expression of HIF-1α and mTOR. RESULTS: Endometriotic glands showed significant cytoplasmic expression of both markers in patients with poor ovulation, severe endometriosis, and infertile for >2 years ( P <0.001). Also, patients with intense and worst pain show significant immunohistochemical expression of both markers ( P <0.001). There is a significant correlation between mTOR and HIF-1α expression in endometriotic tissue samples as P <0.001. CONCLUSIONS: Our data suggest that both mTOR and its downstream target HIF-1α transcription factor are both disrupted in patients with endometriosis, which is consistent with aberrant activation of these pathways and their possible contribution to the pathogenesis of endometriosis. These results could offer a promising novel opportunity to be blocked therapeutically. As new management options need to be refined in particular in severe cases and infertile patients with endometriosis, therefore future studies are warranted to investigate treating endometriosis with mTOR inhibitors; the latter are already in clinical trials in phase III and IV, treating solid tumors as well as non-neoplastic disorders.

A feasible HPTLC method for concurrent quantitation of allopurinol-montelukast co-therapy in plasma and evaluation of their hepatic and renal effects in rats: Analytical, biochemical, and histopathological study.

Recent studies presented the crucial role of montelukast (MON, a leukotriene receptor antagonist) against gouty arthritis and its protective effect on drug-induced liver and kidney injury. Allopurinol (ALO, a selective xanthine oxidase inhibitor) is also used for treatment of hyperuricemia, however, it induces hepatotoxicity and acute kidney injury. Therefore, this study introduces the first analytical/biochemical/histopathological assay for MON-ALO co-therapy and aims to: inspect the hepatic and renal impacts of ALO, MON and their combination in rats via biochemical and histopathological examinations, propose and validate a facile HPTLC method for concurrent estimation of ALO-MON binary mixture in human plasma, and employ this method to attain the targeted drugs in real rat plasma. First, the cited drugs in human plasma were simultaneously separated utilizing silica gel G 60 F254-TLC plates. The separated bands were scanned at 268 nm demonstrating appropriate linearities (50.0-2000.0 ng band-1 for each drug) and correlations (0.9986 and 0.9992 for ALO and MON, correspondingly). The calculated detection and quantitation limits, as well as recoveries confirmed the method's reliability. This procedure was validated, and the stability studies were achieved according to Bioanalytical Method Validation Guideline. This work was extended to investigate the possible hepatic and renal effects of ALO, MON and their co-therapy in rats. Using rat's gastric tube, the following was administered to four groups of male Wistar rats: Group Ia and Ib as control (received either saline or DMSO), Groups II, III, and IV were given MON, ALO, and MON+ALO, respectively. Good correlation between the measured biochemical parameters and the observed histopathological changes was encountered. Considerable drop in aspartate transaminase and alanine transaminase levels, in addition to lower liver damage changes were observed in the combination group compared to MON or ALO-treated groups. Regarding renal changes, ALO-MON co-therapy caused elevation in the serum creatinine and blood urea nitrogen levels when compared to controls and MON- or ALO-treated groups. Severe proteinaceous casts accumulation in kidney tubular lumen, severe congestion, and severe tubular necrosis were also noticed in the combination group. Lastly, this study suggests ALO-MON co-treatment not only as a preventive therapy against gouty arthritis but also as a new line to minimize ALO-induced hepatic injury. However, co-administration of ALO and MON should be further studied to assess the benefits and risks in various tissues, adjust the MON dosing, and monitor its nephrotoxic effect.

Protective effects of curcumin and Ginkgo biloba extract combination on a new model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative illnesses, and yet, no workable treatments have been discovered to prevent or reverse AD. Curcumin (CUR), the major polyphenolic compound of turmeric (Curcuma longa) rhizomes, and Ginkgo biloba extract (GBE) are natural substances derived from conventional Chinese herbs that have long been shown to provide therapeutic advantages for AD. The uptake of curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Meanwhile, GBE has been shown to improve BBB permeability. The present study evaluated the neuroprotective effects and pharmacokinetic profile of curcumin and GBE combination to find out whether GBE can enhance curcumin's beneficial effects in AD by raising its brain concentration. Results revealed that CUR + GBE achieved significantly higher levels of curcumin in the brain and plasma after 30 min and 1 h of oral administration, compared to curcumin alone, and this was confirmed by reversed phase high-performance liquid chromatography (RP-HPLC). The effect of combined oral treatment, for 28 successive days, on cognitive function and other AD-like alterations was studied in scopolamine-heavy metal mixtures (SCO + HMM) AD model in rats. The combination reversed at least, partially on the learning and memory impairment induced by SCO + HMM. This was associated with a more pronounced inhibitory effect on acetylcholinesterase (AChE), caspase-3, hippocampal amyloid beta (Aß1-42), and phosphorylated tau protein (p-tau) count, and pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukine-1beta (IL-1ß), as compared to the curcumin alone-treated group. Additionally, the combined treatment significantly decreased lipid peroxidation (MDA) and increased levels of reduced glutathione (GSH), when compared with the curcumin alone. These findings support the concept that the combination strategy might be an alternative therapy in the management/prevention of neurological disorders. This study sheds light on a new approach for exploring new phyto-therapies for AD and emphasizes that more research should focus on the synergic effects of herbal drugs in future.

Which data subset should be augmented for deep learning? a simulation study using urothelial cell carcinoma histopathology images.

BACKGROUND: Applying deep learning to digital histopathology is hindered by the scarcity of manually annotated datasets. While data augmentation can ameliorate this obstacle, its methods are far from standardized. Our aim was to systematically explore the effects of skipping data augmentation; applying data augmentation to different subsets of the whole dataset (training set, validation set, test set, two of them, or all of them); and applying data augmentation at different time points (before, during, or after dividing the dataset into three subsets). Different combinations of the above possibilities resulted in 11 ways to apply augmentation. The literature contains no such comprehensive systematic comparison of these augmentation ways. RESULTS: Non-overlapping photographs of all tissues on 90 hematoxylin-and-eosin-stained urinary bladder slides were obtained. Then, they were manually classified as either inflammation (5948 images), urothelial cell carcinoma (5811 images), or invalid (3132 images; excluded). If done, augmentation was eight-fold by flipping and rotation. Four convolutional neural networks (Inception-v3, ResNet-101, GoogLeNet, and SqueezeNet), pre-trained on the ImageNet dataset, were fine-tuned to binary classify images of our dataset. This task was the benchmark for our experiments. Model testing performance was evaluated using accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve. Model validation accuracy was also estimated. The best testing performance was achieved when augmentation was done to the remaining data after test-set separation, but before division into training and validation sets. This leaked information between the training and the validation sets, as evidenced by the optimistic validation accuracy. However, this leakage did not cause the validation set to malfunction. Augmentation before test-set separation led to optimistic results. Test-set augmentation yielded more accurate evaluation metrics with less uncertainty. Inception-v3 had the best overall testing performance. CONCLUSIONS: In digital histopathology, augmentation should include both the test set (after its allocation), and the remaining combined training/validation set (before being split into separate training and validation sets). Future research should try to generalize our results.

The combination of olive oil and Lepidium sativum improves the deleterious effects resulting from dexamethasone-induced osteoporosis in rats.

INTRODUCTION: Osteoporosis is characterized by deterioration of bone microarchitecture and reduced bone mass and can increase the risk of fracture. To reduce this risk, the aim of this study was to compare the combination effects of olive oil and Lepidium sativum compared to the conventional drug therapy alendronate. METHODS: Osteoporosed-induced rat model was established by administration of dexamethasone in female adult albino rats. The serum level of Ca2+, P3+, and osteocalcin was assessed. In addition, histopathological changes and immunohistochemical expression of osteopontin within bone specimens were performed. RESULTS: Our results showed that a combination of olive oil and Lepidium sativum had a beneficial therapeutic effect in the treatment of osteoporosis as compared to alendronate therapy. This was demonstrated by increase of serum Ca2+, P3+, and osteocalcin levels in treated compared to control groups. Intriguingly, the highest effect was noticed in rats that received a combination of olive oil and Lepidium sativum compared to the individual treatment. This was reflected by an increase in the cortical bone thickness and a decrease in immunohistochemical expression of osteopontin compared to individual treated groups. CONCLUSION: We concluded that the administration of a combination of olive oil and Lepidium sativum improves bone mineral health and intensity and reduces the risk of osteoporosis in a rat model.

Effects of furosemide and tadalafil in both conventional and nanoforms against adenine-induced chronic renal failure in rats.

BACKGROUND: Chronic renal failure (CRF) is a progressive loss of renal function that lead to reduced sodium filtration and inappropriate suppression of tubular reabsorption that ultimately leads to volume expansion. The aim of this study was to study the efficacy of furosemide and tadalafil nanoforms compared to conventional forms against adenine-induced CRF rat-model. METHODS: Addition of 0.75% adenine to the diet of rats for 4 weeks gained general acceptance as a model to study kidney damage as this intervention mimicked most of the structural and functional changes seen in human chronic kidney disease Urine analysis, histopathological changes and immunohistochemical expression of caspase-3 and interleukin-1 beta (IL-1ß) in renal tissues were performed. RESULTS: Our results showed that the combination of tadalafil and furosemide using conventional and nanoparticle formulations had better renoprotective effect than individual drugs. This was demonstrated by improvement of urinary, serum and renal tissue markers as indicative of organ damage. This was also reflected on the reduction of tubular expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Immunohistochemical studies showed that the deteriorated renal cellular changes indicated by increased expression of caspase-3 and IL-1ß were greatly improved by the combined treatment particularly with the nanoforms. CONCLUSIONS: The nanoforms of both furosemide and tadalafil had greater renopreventive effects compared with conventional forms against adenine-induced CRF in rats.

Celecoxib has Preventive and Therapeutic Benefits against Nephrotoxicity Caused by Gentamicin in Mice.

It's crucial to comprehend the impact of oxidative stress and pro-inflammatory cytokines in the gentamicin-induced kidney injury mechanism. Celecoxib was administered orally either before or after intraperitoneal therapy with gentamicin in mice. The serum levels of creatinine (SCr), blood urea nitrogen (BUN), IL-6, and TNF-α were measured by ELISA test, as well as the levels of the kidney tissue malondialdehyde (MDA), and glutathione (GSH) were also estimated spectrophotometrically. The renal expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cyclooxygenase 2 (COX-2) mRNAs were evaluated by qPCR. Histopathological evaluation and Immunohistochemical examination of kidney NF-κB, IL-6, and COX-2 were also, performed. Celecoxib successfully prevented gentamicin-induced kidney damage as indicated by reducing blood BUN, SCr, and tissue MDA levels and increasing renal tissue GSH levels as well as lowering the blood IL-6 and TNF-α in comparison to mice received gentamicin. Furthermore, celecoxib has inhibited COX-2, NF-κB, IL-6, and TNF-α expression in the renal tissue. It is noteworthy that celecoxib therapy after gentamicin administration brought about substantially the same results as celecoxib treatment before gentamicin injection in mice. Our results showed the role of celecoxib as a therapeutic tool for gentamicin-induced nephrotoxicity as well as raised its beneficial prophylactic role in this medical challenge by attenuating oxidative stress and inflammation.

The Effects of Commercially Available Syzygium aromaticum, Anethum graveolens, Lactobacillus acidophilus LB, and Zinc as Alternatives Therapy in Experimental Mice Challenged with Cryptosporidium parvum.

BACKGROUND: Waterborne cryptosporidiosis is the second cause of diarrhea in young children and immunocompromised hosts after rotavirus. Except for nitazoxanide (NTZ), there is no accredited cryptosporidiosis treatment to date. Therefore, there is an urgent need to find an effective and safe treatment for cryptosporidiosis. This study aimed to investigate the possible anti-protozoal effects of Syzygium aromaticum (clove) oil, Anethum graveolens (dill) seeds oil, Lactobacillus acidophilus LB, and zinc against Cryptosporidium parvum in comparison to NTZ. METHODS: Besides the negative control, mice from six experimental groups (T1-T6) were infected with Cryptosporidium parvum oocysts. On the seventh day post-infection (PID), mice from five groups were treated for 8 consecutive days with NTZ, clove oil, dill seed oil, Lactobacillus acidophilus LB, and zinc commercial forms (T2-T5). Oocysts shedding rate, differences of mice body weight, serum IL10, and TNF-α, cryptosporidial antigen, and cd3 at the intestinal mucosa were evaluated at the end of the experiment. RESULTS: The mean of the C. parvum oocysts' shedding rate was significantly lower in all treated groups than in the non-treated group. The oocysts reduction rate was the highest in zinc-treated mice (98.3%), Lactobacillus acidophilus LB and dill-treated groups (95.77%), and the NTZ-treated group (91.55%). Clove oil was the least effective, with a 74.65% reduction rate. Excluding the clove oil-treated group, immunohistochemical analysis revealed the clearance of the Cryptosporidium antigen in the intestinal tissue in all treated groups. CONCLUSION: The study has provided a rational basis for using these safe, cheap, and commercially available alternatives in treating cryptosporidiosis combined with NTZ.

Transmembrane and Tetratricopeptide Repeat Containing 4 Is a Novel Diagnostic Marker for Prostate Cancer with High Specificity and Sensitivity.

The histopathologic diagnosis of prostate cancer (PCa) from biopsies is a current challenge if double or triple staining is needed. Therefore, there is an urgent need for development of a new reliable biomarker to diagnose PCa patients. We aimed to explore and compare the expression of TMTC4 in PCa cells and tissue specimens and evaluate its sensitivity and specificity. The expression of TMTC4 in PCa and normal prostate epithelial cells was determined by real-time PCR and Western blot analyses. Immunohistochemical (IHC) staining of TMTC4 was performed on tissues collected from PCa and benign prostatic hyperplasia (BPH). Our results show a high expression of TMTC4 on mRNA and protein levels in PCa versus BPH1 and normal cells (p < 0.05). IHC results show strong cytoplasmic expressions in PCa cases (p < 0.001) as compared to BPH cases. The overall accuracy as measured by the AUC was 1.0 (p < 0.001). The sensitivity and specificity of the protein were 100% and 96.6%, respectively. Taken together, we report a high TMTC4 expression in PCa cells and tissues and its ability to differentiate between PCa and BPH with high sensitivity and specificity. This finding can be carried over to clinical practice after its confirmation by further studies.

Valproate attenuates hypertonic glycerol-induced rhabdomyolysis and acute kidney injury.

BACKGROUND AND AIM: The current study investigated the effects of treatment with 300 mg/kg valproic acid on rhabdomyolysis and acute kidney injury induced by intramuscular injection of hypertonic glycerol in rats. METHODS: Four groups of male wistar rats: control and hypertonic glycerol, valproic acid and valproic acid + hypertonic glycerol treated groups were used. Blood urea nitrogen, serum creatinine, creatinine kinase (CK) and CK MB, myoglobin and renal reduced glutathione (GSH) levels were measured. Histopathological examination of the kidneys was carried out to evaluate the degree of renal injury in each group. The expression of interleukin-1 beta "IL-1ß" in renal tissue was detected using immunohistochemistry. RESULTS: Hypertonic glycerol administration led to severe renal tubular damage with a significant elevation of blood urea nitrogen, serum creatinine, creatinine kinase, CK MB and myoglobin levels and overexpression of IL-1ß compared to control group. Valproic acid administration attenuated both the muscle injury and the acute kidney injury induced by hypertonic glycerol, estimated through a significant reduction of creatinine kinase, myoglobin, and serum creatinine. Valproic acid administration caused a significant increase in GSH in the hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group. A significant decrease in tubular necrosis grade, and expression of IL-1ß in hypertonic glycerol + valproic acid group compared to the hypertonic glycerol group was observed. CONCLUSION: This study demonstrates, for the first time to the best of our knowledge, that valproic acid could ameliorate the rhabdomyolysis and the related acute kidney injury in rats.

Multiparametric transvaginal ultrasound in the diagnosis of endometrial cancer in post-menopausal bleeding: diagnostic performance of a transvaginal algorithm and reproducibility amongst less experienced observers.

OBJECTIVE: (a) To comparatively evaluate the performance of grayscale ultrasound features, power Doppler (PD) blood flow characteristics, and gel infusion sonography (GIS) in diagnosing endometrial cancer during real-time examination, (b) to compare the performance of real-time diagnosis of endometrial cancer by experienced observers with offline analysis by blinded observers using similar sonographic criteria during review of cine loop clips. METHODS: 152 females with post-menopausal bleeding (PMB) had ET ≥ 4 mm at first-line ultrasound were included. Two experienced radiologists evaluated endometrial patterns at real-time evaluation (grayscale ultrasound, PD, and GIS), then examinations were stored as video clips for later evaluation by two less-experienced radiologists. The reference standard was hysteroscopy (HY) and/or hysterectomy with the histopathological examination. The area under (AUC) the receiver operating characteristic (ROC) curve was calculated to assess the diagnostic performance for the prediction of endometrial cancer. RESULTS: Among 152 females with ET ≥ 4 mm at first line TVUS, 88 (57.9%) patients had endometrial cancer on final pathologic analysis. Real-time ultrasound criteria (ET ≥ 5 mm with the presence of irregular branching endometrial blood vessels or multiple vessels crossing EM or areas with densely packed color-splash vessels with non-intact or interrupted EMJ at the grayscale ultrasound and/or GIS) correctly diagnosed 95% of endometrial cancers with 92% diagnostic efficiency.There is comparable accuracy of real-time evaluation (96%) and offline analysis (92%) after the exclusion of poor quality videos from the analysis. The diagnostic criteria showed good to an excellent agreement between real-time ultrasound and offline analysis. CONCLUSION: When real-time ultrasound is performed with good technique, utilizing multiple parameters, it is possible to diagnose endometrial cancer with a high degree of accuracy and reproducibility. ADVANCES IN KNOWLEDGE: when real-time ultrasound is performed with good technique, utilizing multiple parameters, it is possible to diagnose endometrial cancer with a high degree of accuracy and reproducibility.

Intralesional verapamil in the treatment of keloids: A clinical, histopathological, and immunohistochemical study.

INTRODUCTION: The histopathological changes and immunohistochemical studies occurring in keloids in vivo after treatment by intralesional (IL) verapamil are not yet assessed. This study aimed to evaluate the efficacy and safety as well as the histological/immunohistochemical effects of intralesional verapamil on keloids. PATIENTS AND METHODS: Thirty-one patients with 43 keloids were treated with IL verapamil at 3-week intervals until reaching complete flattening of the lesion or for a maximum of 6 sessions. Keloid biopsies were obtained before and after treatment for evaluation of histopathological changes and the immunohistochemical expression of VEGF and MMP9. RESULTS: Of 43 keloids, 6 keloids (14%) and 17 (39.5%) showed excellent and good improvement, respectively, with no significant side effects except for pain at the site of injection. Histopathological and immunohistochemical evaluations were consistent with the clinical observations after treatment, and there was a statistically significant decrease in VEGF and MMP9 expressions after treatment. CONCLUSION: IL verapamil is effective in the treatment of keloids which is possibly attributed to suppression of MMP9 and VEGF. It is a simple and relatively safe treatment method for keloids.

Evidences of brain and lung invasion of a local water Cryptosporidium parvum isolate in comparison to Iowa strain: serological and immunohistochemical cytokine evaluation.

Cryptosporidium spp. is an obligate intracellular parasite that has become a community threat. The pathological consequences of cryptosporidiosis vary not only in different Cryptosporidium species but even among different isolates of the same species. The present study aimed to track the serological and immunohistopathological differences between animals infected by Cryptosporidium parvum "Iowa isolate" (CPI) and Cryptosporidium parvum "water isolate" isolated from a local water supply in Assiut Governorate, Egypt (CPW). Three experimental groups were encountered: negative control group (C), the CPI group and the CPW group; each contains ten Swiss albino mice. Serum cytokine: IL10 and TNF-α were measured. Expression of Cryptosporidium antigen and CD3 in the intestinal, pulmonary and brain tissue were evaluated through immunohistochemical assay. IL10 and TNF-α were elevated in both infected groups, over expression of Cryptosporidium protein and CD3 in the intestinal, pulmonary and brain tissue in CPW infected group compared to Iowa infected one. Multi-organs affection occurred in the CPW indicating more severe pathogenicity and virulence than standard Iowa isolate. The local C. parvum isolate was more virulent than tested Iowa isolate as it spread extra-intestinally to reach brain tissue.

Pregabalin administration and withdrawal affect testicular structure and functions in rats.

The aim of this prospective experimental study was to investigate the effects of pregabalin (PG) administration and withdrawal on testicular structures and functions in rats. A total of 24 male Wistar rats were divided into two groups (n = 12 each): a control group received normal saline, and PG-treated group received 62 mg kg-1  day-1 PG for 2 months. Half the animals of each group were sacrificed for the collection of blood and testicular samples. The remaining animals were bred for another 2 months without treatment before collection of blood and testicular samples. PG administration decreased testosterone and increased luteinising hormone (LH) and follicle-stimulating hormone (FSH) levels versus controls. PG withdrawal led to a decrease in both FSH and LH and an increase in testosterone levels versus saline withdrawal. Compared to controls, PG administration caused degeneration of seminiferous tubules and decreased the number of spermatogenic but increased the number of Leydig cells. After PG withdrawal, these cells showed a rebound reverse. Reduced glutathione levels increased with PG administration while PG withdrawal increased malondialdehyde levels. Conclusion: PG administration affected testicular morphometry, gonadotrophic and sex hormones; however, there was a rebound reversal in all these parameters and a significant oxidative stress in PG withdrawal.

Vitamin D receptor and cellular retinol-binding protein-1 immunohistochemical expression in normal, hyperplastic and neoplastic endometrium: Possible diagnostic and therapeutic implications.

BACKGROUND: We conducted this study to assess the effect of VDR and CRBP-1 immunohistochemical expression on the endometrium and to explore their role in endometrial cancer carcinogenesis. METHODS: This study comprised two hundred paraffin-embedded endometrial tissue samples diagnosed as 42 and 63 proliferative and secretory endometrium respectively, 45 endometrial hyperplasias with atypia and 50 endometrial carcinomas (25 low-grade and 25 high-grade endometrial carcinomas). The immunohistochemical method was done to determine the expression of VDR and CRBP-1. RESULTS: VDR was strongly expressed in 8 (17.8%) cases with endometrial hyperplasia, 15 (60%) cases with low-grade endometrial carcinoma, and 22 (88%) cases with high-grade endometrial carcinoma. While CRPB1 overexpression was noted in cases with proliferative endometrium, secretory endometrium and endometrial hyperplasia with atypia, 37 (88.1%), 56 (88.9%) and 3 (6.7%) cases respectively and all malignant cases showed negative expression. CONCLUSIONS: Increased VDR expression and reduced CRBP-1 expression are associated with malignant features of the endometrium with a significant statistical difference of immunoreactivity between groups of normal endometrium, hyperplastic changes & carcinoma. Our data suggested that increased VDR expression is partly associated with endometrial cancers through a premalignant phase. Also, increased VDR and reduced CRBP-1 expression are associated with the progression of endometrial carcinoma with higher grades.

Is bronchoscopic view a reliable method in diagnosis of tracheobronchial aspergillosis in critically ill non-neutropenic patients?

INTRODUCTION: Pulmonary aspergillosis is the main respiratory fungal infection however; its diagnosis is missed or delayed in critically ill non-neutropenic patients. Despite the utility of fiberoptic bronchoscopy for the evaluation of tracheobronchial aspergillosis (TBA) in immunocompromised patients has been extensively studied, however its utility in critically ill non-neutropenic patients is underestimated. OBJECTIVES: To assess the bronchoscopic changes suspected TBA relative to the microbiological and histopathological aspects in critically ill non-neutropenic patients admitted to respiratory intensive care unit (RICU). METHODS: We prospectively studied 139 critically ill non-neutropenic patients admitted to RICU and had a clinical suspicion of broncho-pulmonary Aspergillus infection. Those patients were subjected to clinical and bronchoscopic assessment for the evaluation of suspected TBA. Microbiological culture of bronchoalveolar lavage (BAL) and histopathological examination of tracheobronchial biopsies were done. RESULTS: Bronchoscopic changes suspected TBA were found in 48.2% of patients (67/139), where Aspergillus infection was confirmed microbiologically in 59.7% (40/67) and histopathologically in 56.7% (38/67). Of these changes, whitish plaques ± ulcers, pseudomembrane and/or sticky secretion with hyperemic mucosa were detected in 68.7%, 26.9% and 16.4% respectively. These changes were mostly seen in the main bronchi (54/67; 80.6%). The sensitivity, specificity, positive, negative predictive values and overall accuracy of these bronchoscopic changes as compared with BAL fluid results were 83.3%, 70.3%, 53.2%, 91.2% and 74.1% respectively. CONCLUSIONS: Bronchoscopy could be a reliable procedure for TBA diagnosis in critically ill non-neutropenic patients. Whitish plaques ± ulcers were the prominent bronchoscopic changes with reasonable diagnostic accuracy for prediction of TBA.

Prognostic and Predictive Role of Excision Repair Cross-complementation Group 1 and Thymidylate Synthase in Colorectal Carcinoma Patients Received FOLFOX Chemotherapy: An Immunohistochemical Study.

BACKGROUND AND STUDY AIMS: We aim to determine the frequency of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC-1) immunohistochemical (IHC) expression and its relationship with clinicopathologic variables in colorectal carcinoma (CRC) patients. In addition, we aim to assess the correlation between TS and ERCC-1 expression and the response of these cases to oxaliplatin and 5-fluorouracil chemotherapy (FOLFOX). PATIENTS AND METHODS: Fifty-one CRC patients were prepared for IHC analysis of ERCC-1 and TS protein expression. All patients received oxaliplatin and 5-fluorouracil combined chemotherapy (FOLFOX) and were followed up for 24 months. RESULTS: The data analysis showed that high ERCC-1 and TS expression was significantly associated with early treatment failure (P=0.020 and 0.000). In contrast, TS immunoexpression affects the disease-free survival rate (P=0.010). The presence of deep tumor invasion, distant metastasis, lymph node metastasis, and high Dukes' classification were significantly statistically associated with early treatment failure (P=0.001, 0.000, 0.041, and 0.015, respectively). CONCLUSIONS: Our results showed that both ERCC-1 and TS are predictive factors for early treatment failure in CRC patients. TS protein is a prognostic factor for disease-free survival rates. This supports the theory that both ERCC-1 and TS can be used to improve chemotherapeutic outcomes in CRC patients. High expression of TS and ERCC-1 helps in the identification of cases that will get fewer benefits from FOLFOX chemotherapy. As an innovative strategy, in these cases, we can use alternative chemotherapeutic regimens or add an extra agent. In addition, Dukes' classification and lymph node metastasis are predictive factors for early treatment failure. Thus, all those values can be used to predict CRC patients with bad prognosis and those who will get fewer benefits from FOLFOX.

Pharmaceutical, clinical, and immunohistochemical studies of metformin hydrochloride topical hydrogel for wound healing application.

Wound healing could be categorized as a chronic disorder which needs a prompt and effective medication. Nowadays, vascular problems and wound-healing progression studies relay on the role of metformin; however, the exact mechanisms for its beneficial effects are still not completely understood. The aim of the present work was to study the potential of metformin hydrochloride, MET-HCL hydrogel in wound healing after topical administration. MET-HCL hydrogel was formulated using different hydrogel bases then characterised for its drug content and pH, homogeneity, viscosity, spreadability, and in vitro release. Furthermore, the wound-healing activity was evaluated in rats. Clinical study was also performed in patients showing lower limbs traumatic wounds and cutaneous ulcers. In addition, histopathology and immunohistochemical studies were also investigated. Results showed that MET-HCL hydrogels have a high drug content, and they are homogenous and spreadable with minimum sheer stress and showed null irritation. Furthermore, carbopol showed the optimum gel base for the highest MET-HCL release. Wound healing activity in rats showed a significant (p < 0.05) increase in the percentage wound contraction from the day-7 compared with plain hydrogel. Clinical study revealed a complete healing of traumatic wounds and cutaneous ulcers after 21 and 30 days, respectively. Moreover, histopathology investigation showed a complete restoration of connective tissue matrix and re-epithelization of the induced wound. In addition, immunohistochemistry showed a significant expression of transforming growth factor-ß1 (TGF-ß1). In conclusion, MET-HCL hydrogel is a promising formulation for topical treatment of wounds with effective and faster healing activity.