Incidentally found metastatic prostatic carcinoma in a therapeutic orchiectomy specimen

Metastatic tumour involving the testis is a rare event. Incidental discovery of metastatic cancer in a therapeutic orchiectomy is even rarer. We report a case of metastatic adenocarcinoma prostate found incidentally in one of the bilateral therapeutic orchiectomy specimens. The patient was a 55-year-old man presenting with back ache and generalized body aches. Clinical examination showed malignant feel of prostate. Bone scan revealed metastatic disease and a serum PSA level of \u3e100 ng/ml. Clinical diagnosis of carcinoma prostate was established and subsequent bilateral orchiectomy for hormonal deprivation was performed. On gross examination of left testis, there was a small 0.7 X 0.6 cm suspicious area. Microscopically, this area showed an infiltrating tumour in the interstitium with entrapped seminiferous tubules. Focal intravascular tumour deposit was also noted. Immunohistochemical stain for prostate-specific antigen was positive in the tumour, which confirmed the diagnosis of metastatic prostate adenocarcinoma

Prevalence of Hepatitis C Virus Infection among Chronic Kidney Disease Patients on Regular Hemodialysis

OBJECTIVES To determine the frequency of the Hepatitis C Virus in patients with chronic kidney disease receiving regular hemodialysis. METHODOLOGY At a tertiary care hospital in Peshawar, 211 patients were observed to ascertain the frequency of the Hepatitis C Virus in chronic kidney disease patients receiving regular hemodialysis. The technique of non-probability sequential sampling was employed to acquire samples. SPSS version 26.0 was used. RESULTSAmong the CKD patients with Hepatitis C Virus (HCV) infection, a higher proportion of males (48.5%) tested positive compared to females (28.1%). Furthermore, the prevalence of HCV infection was significantly higher in CKD patients residing in urban areas (98.5%) compared to those in rural areas (1.5%). The statistical analysis indicated a significant association between the prevalence of Hepatitis and the factors of gender and residency (P value = 0.002). Out of 211, hepatitis C-positive patients 66.2% were diabetics and hypertensive were 77.9%. CONCLUSION Hospitalized CKD patients have a considerably higher frequency of hepatitis C infection. To stop the spread of the hepatitis C virus, nephrology wards should undertake strict universal infection control procedures

Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri

Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet–visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood–brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections

Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba

Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major endproduct in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time

Rising burden of Hepatitis C Virus in hemodialysis patients

<p>Abstract</p> <p>Aim</p> <p>High prevalence of Hepatitis C virus (HCV) has been reported among the dialysis patients throughout the world. No serious efforts were taken to investigate HCV in patients undergoing hemodialysis (HD) treatment who are at great increased risk to HCV. HCV genotypes are important in the study of epidemiology, pathogenesis and reaction to antiviral therapy. This study was performed to investigate the prevalence of active HCV infection, HCV genotypes and to assess risk factors associated with HCV genotype infection in HD patients of Khyber Pakhtunkhwa as well as comparing this prevalence data with past studies in Pakistan.</p> <p>Methods</p> <p>Polymerase chain reaction was performed for HCV RNA detection and genotyping in 384 HD patients. The data obtained was compared with available past studies from Pakistan.</p> <p>Results</p> <p>Anti HCV antibodies were observed in 112 (29.2%), of whom 90 (80.4%) were HCV RNA positive. In rest of the anti HCV negative patients, HCV RNA was detected in 16 (5.9%) patients. The dominant HCV genotypes in HCV infected HD patients were found to be 3a (n = 36), 3b (n = 20), 1a (n = 16), 2a (n = 10), 2b (n = 2), 1b (n = 4), 4a (n = 2), untypeable (n = 10) and mixed (n = 12) genotype.</p> <p>Conclusion</p> <p>This study suggesting that i) the prevalence of HCV does not differentiate between past and present infection and continued to be elevated ii) HD patients may be a risk for HCV due to the involvement of multiple routes of infections especially poor blood screening of transfused blood and low standard of dialysis procedures in Pakistan and iii) need to apply infection control practice.</p

Diagnostic Accuracy of Clinical Tests in Knee Joint Injuries: A Single Centered Experience

OBJECTIVES: The accuracy of clinical tests (Lachman, McMurray, Anterior Drawer) in the diagnosis of knee joint injuries in comparison to arthroscopy taken as gold standard. METHODOLOGY: This cross-sectional study was conducted at the Department of Orthopedic Surgery, Khyber Teaching Hospital, Peshawar for 3 years. Total of 48 patients were recruited in the study. Data was collected after ethical approval from the hospital ethical committee using consecutive non-probability sampling techniques. Written informed consent was obtained from the patients. Arthroscopy examination was taken as a gold standard. Data analysis was performed using statistical software SPSS 21 and MEDCALC online software for calculating sensitivity and specificities of the clinical tests. RESULTS: Mean age was 26.4+6.5 years. Lachman and Anterior Drawer tests were noted to have 91.67% and 66.67% sensitivity for anterior cruciate ligament while McMurray test was noted only 66.67% sensitive for both meniscal injuries. On the other hand, Lachman was 95.8% specific, McMurray was 77.78%, and Anterior Drawer was 79.2% specific. Regarding accuracy, Lachman was 93.7%, McMurray 70.8% and Anterior Drawer was 72.9% accurate. CONCLUSION: Among clinical examination and specific examination tests, Lachman has high sensitivity, specificity and accuracy followed by Anterior Drawer test and MacMurray for diagnosing anterior cruciate ligament and meniscal injuries of knee joint

Patient satisfaction following short segment fusion with posterior instrumentation in thoracolumbar fractures

Background: This retrospective study assesses patient satisfaction following short-segment fusion with posterior instrumentation in thoracolumbar fractures. A total of 100 patients were enrolled in the study, which was conducted in the Department of Orthopedic KTH Hospital in Peshawar from January 2020 to January 2021. The patients were followed up at 6 weeks, 3 months and 6 months post-operatively. The satisfaction score was assessed using a visual analog scale (VAS) and divided into four categories: very satisfied, satisfied, dissatisfied and very dissatisfied. The results showed that 81% of the patients were very satisfied and 19% were satisfied with the procedure. The mean VAS score was 8.58 ± 0.67. No significant differences were found in the satisfaction scores between male and female patients (p=0.731). This study provides valuable insight into the effectiveness of short segment fusion with posterior instrumentation in the treatment of thoracolumbar fractures and highlights the importance of post-operative follow-up in determining patient satisfaction. Objection: The study provides valuable insight into the effectiveness of short-segment fusion with posterior instrumentation in the treatment of thoracolumbar fractures and highlights the importance of postoperative follow-up in determining patient satisfaction

Brain-eating Amoebae Infection: Challenges and Opportunities in Chemotherapy

Pathogenic free-living amoeba are known to cause a devastating infection of the central nervous system and are often referred to as “brain-eating amoebae”. The mortality rate of more than 90% and free-living nature of these amoebae is a cause for concern. It is distressing that the mortality rate has remained the same over the past few decades, highlighting the lack of interest by the pharmaceutical industry. With the threat of global warming and increased outdoor activities of public, there is a need for renewed interest in identifying potential anti-amoebic compounds for successful prognosis. Here, we discuss the available chemotherapeutic options and opportunities for potential strategies in the treatment and diagnosis of these life-threatening infections

Nanovehicles in the improved treatment of infections due to brain-eating amoebae

Pathogenic free-living amoebae are known to cause fatal central nervous system infections with extremely high mortality rates. High selectivity of the blood–brain barrier hampers delivery of drugs and untargeted delivery of drugs can cause severe side effects. Nanovehicles can be used for targeted drug delivery across the blood–brain barrier. Inorganic nanoparticles have been explored as carriers for various biomedical applications and can be modified with various ligands for efficient targeting and cell selectivity while lipid-based nanoparticles have been extensively used in the development of both precision and colloidal nanovehicles. Nanomicelles and polymeric nanoparticles can also serve as nanocarriers and may be modified so that responsiveness of the nanoparticles and release of the loads are linked to specific stimuli. These nanoparticles are discussed here in the context of the treatment of central nervous system infections due to pathogenic amoebae. It is anticipated that these novel strategies can be utilized in tandem with novel drug leads currently in the pipeline and yield in the development of much needed treatments against these devastating parasites

Gold-Conjugated Curcumin as a Novel Therapeutic Agent against Brain-Eating Amoebae

Balamuthia mandrillaris and Naegleria fowleri are free-living amoebae that cause infection of the central nervous system, granulomatous amoebic encephalitis (GAE) and primary amoebic meningoencephalitis (PAM), respectively. The fact that mortality rates for cases of GAE and PAM are more than 95% indicates the need for new therapeutic agents against those amoebae. Considering that curcumin exhibits a wide range of biological properties and has shown efficacy against Acanthamoeba castellanii, we evaluated the amoebicidal properties of curcumin against N. fowleri and B. mandrillaris. Curcumin showed significant amoebicidal activities with an AC50 of 172 and 74 μM against B. mandrillaris and N. fowleri, respectively. Moreover, these compounds were also conjugated with gold nanoparticles to further increase their amoebicidal activities. After conjugation with gold nanoparticles, amoebicidal activities of the drugs were increased by up to 56 and 37% against B. mandrillaris and N. fowleri, respectively. These findings are remarkable and suggest that clinically available curcumin and our gold-conjugated curcumin nanoparticles hold promise in the improved treatment of fatal infections caused by brain-eating amoebae and should serve as a model in the rationale development of therapeutic interventions against other infections