Perampanel is a novel drug recently approved as adjunctive therapy in epileptic patients aged 12 years and older who have drug-resistant partial epilepsy with and without secondary generalization. Pharmacological researches revealed that perampanel reduces neuronal excitability by a non-competitive antagonistic activity against the ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors causing modulation of glutamatergic neurotransmission. The pharmacological profile of the drug showed complete absorption following oral administration, and extensive metabolism in the liver by oxidation followed by glucuronidation with an elimination half-life of approximately 53–165 h (average: 105 h), allowing once-daily administration. Randomized placebo-controlled trials demonstrated an effective dose range of the drug, between 4 and 12 mg/day, to significantly reduce seizure frequency in patients with partial-onset seizure that are pharmacoresistant with a favorable tolerability profile. The most frequent adverse events of the drug reported in phase III clinical trials were dizziness, somnolence, fatigue, and headache. However, the data raised from the studies can give a hope that perampanel offers a valuable option as an adjuvant therapy for pharmacoresistant partial-onset and secondarily generalized seizures.

Many non-fusion instrumentation techniques were shown to be effective in controlling the progression of spinal deformity in young children, and maintaining the growth potential of the immature spine. Of these, the Vertical Expandable Prosthetic Titanium Rib (VEPTR) has been approved by the FDA in the treatment of Thoracic Insufficincy Syndrome (TIS) in skeletally immature patients. The aim of this presentation is to demonstrate the effect of expansion thoracoplasty and implantation of a VEPTR in three children with progressive spinal deformity despite previous convex- sided hemiepiphysiodesis. Three patients with progressive congenital thoracic scoliosis, who had previously undergone anterior and posterior convex hemiepiphysiodesis of the thoracic spine at the age of 17 to 36 months, were treated with expansion thoracoplasty of the concavity using the VEPTR device at the age of 5 to 9 years. They were evaluated after a minimum of two years in order to assess the effect of the procedure on the spinal deformity, spinal growth, and chest wall expansion. At the latest follow-up, the Cobb angle of the fused segments, the length of the thoracic spine from T1 o T12, and the Space Availabel for the Lungs (SAL) improved in all three patients. Detailed results are listed in the next table. Thoracic spinal height increased from 11.25 to 15.68 cm in patient 1, from 15.40 to 17.15 cm in patient 2, and from 16.35 to 18.25 cm in patient 3. Sagittal Balance improved from +4.5 cm to neurtral in patient 1, and from +6 cm to +1 cm in patient 2, but deteriorated from -0.5 cm to -1.5 cm in patient 3. Expansion Thoracoplasty and VEPTR implantation seem to be effective in rigid congenital scoliosis even after prior convex-sided hemipepiphysiodesis.

Carbon tetrachloride (CCl4) induces testicular damage, through formation of free-radical metabolites. Molecular chaperone heat shock protein of 70kDa (HSP 70) protects cells from various stresses. This study was designed to investigate the potential role of induction of HSP70 using geranylgeranylacetone (GGA) on testicular damage caused by CCl4. Rats were divided into group I (control group), Group II (CCl4 group) received CCl4 s.c. for 4 weeks, group III received CCl4 s.c. for 4 weeks simultaneously with daily single oral dose of GGA (GGA - treated CCl4 group). Serum testosterone, testicular lactate dehydrogenase (LDH) and alkaline phosphatase (ALP), testicular malondialdehyde (MDA), total nitrite and total antioxidant capacity (T-AOC) were measured. Evaluation of histopathological changes and immunohistochemical HSP70 expression for testicular biopsies were performed. Group II showed lower values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC and greater values of testicular MDA and total nitrite than in control. Testicular morphology showed widening of seminiferous lumen, less spermatogenesis, vacuolization of germinative epithelium. Group III had higher values of gonado-somatic index, serum testosterone, testicular LDH, ALP, T-AOC with less testicular MDA and total nitrite than in group II. They have less damage and restored the altered testicular morphology. Immunohistochemical HSP70 expression was increased in the testicular spermatogenic and sertoli cells in group II that was significantly accentuated in group III. These findings suggest that GGA-induced activation of HSP 70 significantly alleviate CCl4 inflicting testicular damage by HSP 70 mediated cytoprotection and antioxidant effects.

Death receptors 4 and 5 (DR4 and DR5) are cell surface receptors that when activated by their ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in most cancer cells but not in normal cells. Currently, it remains unclear whether DR4 and DR5 are involved in immune surveillance against nonmelanoma skin cancer (NMSC) progression. The aim of this study was to investigate the expression of DR4 and DR5 in NMSC and relate the results to the established clinicopathologic prognostic factors. This study was conducted on about 80 skin specimens from patients with NMSC (40 basal cell carcinoma and 40 squamous cell carcinoma) and diagnosed and confirmed by biopsy. Immunohistochemical analysis for DR4 and DR5 was carried out on formalin-fixed paraffin-embedded sections of skin tissues using avidin-biotin peroxidase method. Significant expression of both DR4 and DR5 was observed in NMSC cases. There was statistically significant association between DR4 and DR5 expression in squamous cell carcinoma and each of tumor site and lymph node metastasis. There was statistically significant association between DR4 expression in basal cell carcinoma and histopathologic subtypes (high expression in nodular type) and between DR5 expression and tumor site (high expression in sun-exposed area). In conclusion, expression of TRAIL receptors that mediate extrinsic apoptotic pathway in NMSC may be suggestive of a reassessment of the suitability of TRAIL-based strategy in future NMSC therapies.

Death receptors 4 and 5 (DR4 and DR5) are cell surface receptors that when activated by their ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in most cancer cells but not in normal cells. Currently, it remains unclear whether DR4 and DR5 are involved in immune surveillance against nonmelanoma skin cancer (NMSC) progression. The aim of this study was to investigate the expression of DR4 and DR5 in NMSC and relate the results to the established clinicopathologic prognostic factors. This study was conducted on about 80 skin specimens from patients with NMSC (40 basal cell carcinoma and 40 squamous cell carcinoma) and diagnosed and confirmed by biopsy. Immunohistochemical analysis for DR4 and DR5 was carried out on formalin-fixed paraffin-embedded sections of skin tissues using avidin-biotin peroxidase method. Significant expression of both DR4 and DR5 was observed in NMSC cases. There was statistically significant association between DR4 and DR5 expression in squamous cell carcinoma and each of tumor site and lymph node metastasis. There was statistically significant association between DR4 expression in basal cell carcinoma and histopathologic subtypes (high expression in nodular type) and between DR5 expression and tumor site (high expression in sun-exposed area). In conclusion, expression of TRAIL receptors that mediate extrinsic apoptotic pathway in NMSC may be suggestive of a reassessment of the suitability of TRAIL-based strategy in future NMSC therapies.

Abstract Background: Thymoquinone (TQ) is the most abundant and active ingredient of Nigella sativa (NS) seeds. Its hepatic, renal, and cardiac protective effects have been demonstrated in animal models. Streptozotocin (STZ) is an antibiotic that is widely used experimentally as an agent capable of inducing insulin-dependent diabetes mellitus (IDDM), also known as type I diabetes mellitus (T1DM). Objectives: This study was carried out in an attempt to highlight the possible beneficial effects of TQ in STZ-induced diabetes in rats and to determine the predictive value of mesenchymal and epithelial markers in the response of diabetic nephropathy to TQ. Materials and Methods: Sixty adult male albino rats were divided in 3 groups: control, diabetic untreated, and diabetic treated with TQ. Results: Diabetic rats exhibited morphological changes in both renal glomeruli and tubules with immunohistochemical expression of the mesenchymal markers Fsp1, desmin, and MMP-17 and disappearance of the epithelial marker ZO-1 largely in the glomeruli of diabetic kidneys. Treatment with TQ significantly attenuated renal morphological and immunohistochemical changes in STZ-induced diabetic rats. Conclusions: Thymoquinone has protective effects on experimental diabetic nephropathy. Both mesenchymal and epithelial markers serve as excellent predictors of early kidney damage and indicators of TQ responsiveness in STZ-induced diabetic nephropathy.

Introduction: Melasma is a common disorder of facial hyperpigmentation that is often difficult to treat and resistant to all treatment modalities and is therefore very frustrating to patients and dermatologists. Objective: Our purpose was to evaluate the efficacy of trichloroacetic acid (TCA) peeling in comparison to double frequency Q-switched (Nd:YAG) laser (1064 nm and 532 nm wavelengths) in treatment of melasma among Egyptian patients. Patients and Methods: A total of 65 adult Egyptian female patients with melasma (age > 18 years old, skin phototypes type III-V) were enrolled in this study. Wood’s light was used for classification of the type of melasma into epidermal, dermal or mixed. The patients were divided into 4 groups: Group 1: Fifteen patients with epidermal melasma were treated with TCA (20%). Group 2: Twenty patients with epidermal, dermal and mixed melasma were treated with TCA (25%). Group 3: Fifteen patients with dermal and mixed melasma were treated with TCA (30%). TCA peeling was performed every 2 weeks up to 8 sessions. Group 4: Fifteen patients were treated with double frequency Q-switched Nd:YAG laser, of whom 7 with epidermal melasma were treated with (532 nm), and 8 with dermal and mixed melasma were treated with (1064 nm). Laser treatment was performed every month up to 6 sessions. The end point of treatment for all patients was the clearance of melasma or occurrence of complications. Melasma area and severity index (MASI) score was used before and after treatment to assess the severity of melasma and evaluate the response of treatment. All patients were followed up monthly for up to 3 months after the end of treatment for possible recurrence. Results: The mean of improvement percentage of MASI score was significantly higher among group 2 treated with TCA 25% compared with other groups (p=0.000***). The epidermal type of melasma was significantly improved compared with the dermal type (p=0.0029***). Group 4 treated with Q-switched Nd:YAG laser (532 nm & 1064 nm) showed the highest complications of post-inflammatory hyperpigmentation (53.3%) compared with other groups. The recurrence of melasma was (32%) among all treated patients. Conclusions: Our findings suggest that TCA peeling is effective in treatment of melasma, TCA 25% was the most effective concentration with rare side effects. Double frequency Q-switched Nd:YAG laser (532 & 1064 nm) is not recommended in treatment of melasma because it was associated with the highest incidence of complications. In our community, the hot climate, the exposure to sunlight and the dark skin types are factors that interfere with the permanent cure of melasma. Therefore, avoidance of sun and heat exposure and the regular use of broad-spectrum sunscreens are essential for melasma patients.