Yellow scorpion (Buthus sinidicus) venom peptides induce mitochondrial-mediated apoptosis in cervical, prostate and brain tumor cell lines.

Scorpion venoms are known to contain over 100,000 biologically active constituents. However, only a few of them have been studied. The major constituents of venom are proteins and peptides, which exhibit various biological and pharmacological properties, including anticancer activities. In the current study, the venom of yellow scorpions (Buthus sindicus) found in Sindh, Pakistan, was extracted and evaluated for its anti-cancer and anti-inflammatory activities. The crude venom showed a dose dependent inhibition of phagocyte oxidative burst from human whole blood cells (28.3% inhibition at highest tested concentration of 300 µg/mL). In-vitro cytotoxicity of crude venom was evaluated against human prostrate (PC3), cervical (HeLa) and neuroblastoma (U87-MG) cell lines, along with cytotoxicity against normal human fibroblast (BJ) cells. Crude venom was cytotoxic to all cell lines, with prominent inhibitory effect on PC3 cells. Crude venom was fractionated through RP-UPLC, resulted in fifteen fractions, followed by evaluation of their anticancer potential. Among all, the fraction I significantly (P < 0.001) reduced the cell viability of all three cancer cell lines, and exhibited insignificant cytotoxicity against normal cell line. Furthermore, the apoptotic cell death pathway was evaluated for crude venom, and fraction I, in most sensitive cell line PC3, by using flow-cytometry analysis. Both crude venom and its fraction I caused a mitochondrial-mediated apoptosis in prostate cancer cells (PC3). To the best of our knowledge, this is the first report of the anticancer and anti-inflammatory activity of venom of Pakistani yellow scorpions. Results indicate their therapeutic potential, and a case for further purification and validation studies.

Epithelial Myoepithelial Carcinoma Masquerading as Simple Parotid Cyst in a Middle Aged Male.

Epithelial-Myoepithelial Carcinoma (EMC) is a very rarely seen biphasic tumour typically seen in older females and constitutes 0.5-1% of all salivary gland neoplasms. The parotid gland is most often involved and occasionally there may be involvement of submandibular and minor salivary glands. Clinical picture often reveals benign nature of the disease. Computed tomography (CT) and magnetic resonance appearances are non-specific and the cytological diagnosis may be challenging, thus more accurate diagnosis can only be made by histological and immunohistochemical study. There is no consensus regarding the optimal treatment of this neoplasm, largely due to its rarity. Wide surgical excision with a clear margin is the treatment of choice because of the tumour's tendency to infiltrate locally. Adjuvant radiotherapy is often required in cases of large primary tumours and positive surgical margins. The tumour may commonly recur locally after resection in 30-50% of cases. We herein present an unusual case of a 46-year-old male who presented with cystic swelling of left parotid gland and diagnosed as EMC on histopathology and immunohistochemical examination. The patient was treated with surgical resection followed by post-operative radiotherapy.

Ears with Cholesteatoma: Outcomes of Canal Wall Up and Down Tympano-Mastoidectomies-A Comparative Prospective Study.

This prospective study has been carried out to observe the outcomes of canal wall up (CWU) and canal wall down (CWD) Tympano-mastoidectomies in ears with cholesteatoma. Outcomes of the procedures have been done in terms of recurrence of cholesteatoma, complications, graft uptake rates and post-operative hearing gain. This study was carried out in the Department of Otorhinolaryngology of a reputed tertiary teaching hospital of North India from January 2016 to June 2020, with a mean follow-up of 32 months. The study included 100 patients of otitis media with cholesteatoma. In Canal Wall Up Tympano-mastoidectomy (CWUT) group, the number of males and females were 22 each. On the other hand, 36 males and 20 females underwent Canal Wall Down Tympano-mastoidectomy (CWDT). Each surgery was done as a single-staged and at the end of the surgical procedure angled oto-endoscopes were used for ensuring complete removal of the disease. Though there is no statistically significant difference in recurrence of cholesteatoma and complications rate in CWU and CWD Tympano-mastoidectomy techniques, but CWUT is superior to CWDT in terms of better graft uptake (p = 0.0156), and better average audiological gain (8.56 ± 0.93 dB) with p value = 0.0315. A diligent post-operative follow-up is must for assessing the outcomes of different types of mastoidectomies. This study shows no statistical difference in the disease recurrence and complication rates between Canal Wall Up and Down Tympano-mastoidectomies, though the anatomical changes and creation of the mastoid cavity in canal wall down procedure may affect the graft uptake and post-operative hearing gain. Use of Oto-endoscopes in cholesteatoma surgery helps in improving the outcomes of both techniques and thus recommended if the facility for the same is available.

Bacteriological and Antibiotic Sensitivity Profile of Cholesteatomatous Otitis Media in Pediatric and Adult Population: Prevailing Scenario in Northern India.

The bacteriological and antimicrobial sensitivity profile of chronic otitis media (COM) varies from region to region and from time to time and may vary among different age group as well. It was against this backdrop of the changing bacteriological profile and sensitivity pattern together with the paucity of categorically separated data of pediatric and adult population, that the present study was undertaken. A total of 193 patients of clinical diagnosis of cholesteatomatous COM with ear discharge and positive culture results were included in the study. Pus sample was collected under aseptic conditions and cultured on solid media and broth. Isolates were identified via standard biochemical tests and sensitivity patterns analysed. Chi square (χ2) test was used to analyse the significance. Pseudomonas was the most common isolate in both the pediatric (37.80%) and adult (51.46%) population. Methicillin sensitive staph aureus (MSSA) was found exclusively in pediatric population (p = 0.003).Piperacillin-Tazobactam combination was the single most effective drug regimen overall. 75% of pseudomonas isolates in pediatric and 87.5% in adults were sensitive to this regimen in vitro. Amikacin was the next most effective drug with 56.69% sensitivity in pediatric and 64.08% sensitivity in adult population. The present study finds piperacillin-tazobactam as the most effective therapy and pseudomonas as the most common isolate in the study population.In order to address the varying and changing bacteriological and sensitivity profile of chronic otitis media occurring among different geographical regions and also within a region over time, the authors recommend its periodic evaluation.

Microbiological Assessment of Chronic Otitis Media: Aerobic Culture Isolates and Their Antimicrobial Susceptibility Patterns.

As there are changing trends in the microbiology of chronic otitis media, this study was carried out to look for the current aerobic microbes and their antimicrobial susceptibilities in patients of chronic otitis media from north Indian region. A total of 322 patients who met the inclusion criteria were studied and aerobic ear swab culture was done under aseptic conditions. Gram staining was performed and antibiotic susceptibility testing was done using Kirby-Bauer disc diffusion method on Mueller-Hinton Agar. A total of 341 culture positive results were obtained from 322 patients. The culture results revealed 10 different aerobic microbes. Gram-positive floras were seen in 152 (44.57%), and Gram-negative in 189(55.43%) isolates. Staphylococcus aureus was the most common isolate present in 131 samples (38.41%), followed by pseudomonas aeruginosa in 101 (29.62%) and proteus in 36 (10.56%). In overall susceptibility of antibiotics against Gram-positive culture isolates, Vancomycin was most effective (97.37%). For Gram-negative microbes, Piperacillin-Tazobactum combination was most effective with overall susceptibility of 79.37% susceptibility. Microbiological assessment of Chronic Otitis Media should be carried out in an area on regular intervals because of the changing patterns of bacteriology and their antimicrobial susceptibilities.

Biosynthesis of silver nanoparticles from Mukia maderaspatana (L) and their biological activities.

Nanotechnology is a field of science that consists of atoms, molecules and supramolecular molecules that create nanoparticles ranging in size from 1-100nm. Silver nanoparticles are widely used that are considered as effective antimicrobial agents. In this paper, the antioxidant activity of biosynthesized SNPs were analyzed by the DPPPH activity, hydrogen peroxide activity, hydroxyl RSA, TAC, TFC; their results confirmed that the phenolic compounds of this plant peels extracts enhanced the antioxidant and antiglycation activity with respect to silver nanoparticles. Biosynthesized nanoparticles of this plant extracts also showed strong zone of inhibition against the different Xanthomas, Pseudomonas and E. coli. This study concluded that biosynthesized nanoparticles of Mukia maderaspatna (M.M) plant peels extracts have the great biological activities i.e. antiglycation, antioxidant and antibacterial. More research is needed to know the exact dose rate and to compare the different dose combination of the plant with the strong antibiotic agents against these bacteria.

Anti-leucine-rich-glioma-inactivated 1 Limbic Encephalitis: An Underrecognised Disease.

Autoimmune limbic encephalitis is a rare autoimmune disease characterised by inflammation of the limbic system of the brain. The disease runs a sub-acute course with cognitive impairment, memory loss and seizures. These patients have been underdiagnosed in Pakistan. Here, we present a case of a middle-aged male, who presented to our Department after having multiple visits to different psychiatrists for his symptoms. The patient had been put on multiple psychiatric and antiepileptic medications, but his condition gradually declined. At our Department, he was thoroughly assessed and then diagnosed as limbic encephalitis on the basis of the typical history, positive anti-leucine-rich-glioma-inactivated 1 (LGI1) antibodies and MRI findings. The patient responded to plasmapheresis and immune modulating therapy and is being followed up. Emphasis is made on early diagnosis; and earlier treatment of such cases, as it holds a substantial importance in management and makes a difference in future outcome. Key Words: Autoimmune limbic encephalitis, Voltage-gated potassium channels, Cognitive dysfunction.

Zygomatico-Coronoid Pseudoarthrosis Due to Osteochandroma of Coronoid Process: A Rare Entity.

INTRODUCTION: Osteochondroma of the coronoid process also known as Jacob's disease, has rarely been reported in the literature and it posses a challenge as diagnosis may be overlooked in favour of other causes of limited mouth opening. CASE REPORT: This is a case report of an adult male patient who presented with restricted mouth opening in whom radiological imaging, especially 3D computed tomography, played a role in establishing the diagnosis of Jacob's disease. CONCLUSION: An osteochondroma of the coronoid process of the mandible (Jacob's disease) is a rare cause of restricted mouth opening and its diagnosis can be overlooked in favour of TMJ ankylosis. The CT scan plays an important role in diagnosis and in planning for surgery.

Simultaneous modelling of coagulant recovery and reuse by response surface methodology.

Surface water from rivers, lakes, reservoirs etc. needs to be treated prior to municipal supplies. The treatment scheme includes coagulation, flocculation, sedimentation, filtration and finally disinfection process. Huge volume of sludge or waste is generated during the coagulation-flocculation. Disposal of the sludge so generated in the treatment plants require careful consideration for managing it sustainably and in an environment friendly manner. Constructive utilization of the inevitable waste may help in finding a sustainable solution to sludge disposal problems. Presently, response surface methodology (RSM) with central composite design (CCD) has been applied to simultaneously model coagulant recovery as well as reuse parameters. In order to simplify the process and increase the applicability, the effect of three significant variables, acid dose, sludge ratio, and recovered coagulant dose are studied. A second order regression model has been developed which gave the optimum combination of acid dose of 30 ml/L, sludge ratio of 1% and recovered coagulant dose of 12 ml/L for maximum turbidity removal. The predicted value of turbidity removal is 95.4%. In the confirmatory experiments, the turbidity removal value was observed to be about 96.2%, which is in good agreement with the predicted value. In addition to turbidity removal, it also helps to effectively remove other impurities from the raw water for it to meet the standards prescribed for potable supply. Thus, the regenerated alum or recovered coagulant has the potential to substitute the conventional coagulants, fully or partially at water treatment plants.

Klippel-Feil Syndrome With Auxiliary Anterior Cervical Meningomyelocele and Thoracic Syringomyelia: A Case Report.

STUDY DESIGN: Case report. OBJECTIVE: Since this is the first ever case of a male patient with Klippel-Feil syndrome (KFS) with anterior cervical meningomyelocele and syringomyelia. All four previously reported cases were female patients. This makes this case unique. SUMMARY OF BACKGROUND DATA: KFS with auxiliary anterior cervical meningomyelocele is a rare entity. To the best of our knowledge so far only four cases are reported. METHODS: A 22-year-old male patient was presented to neurology outpatient department with 2-year history of left hand paresthesia and progressive weakness. The diagnostic evaluation showed KFS with auxiliary anterior cervical meningomyelocele and thoracic syringomyelia. RESULTS: Patient was sent to neurosurgery department for intervention. After discussing the possible risks and complications of intervention he opted for conservative therapy and declined the surgery. CONCLUSION: The paucity of data is the key reason for any recommended protocol for management of such patients but the available literature recommends neurosurgical intervention in symptomatic patients. LEVEL OF EVIDENCE: 5.

Mitomycin-C in Post-endoscopic Septoplasty Synechiae: Does it Really Helps?

Endoscopic septoplasty has advantage of magnified image and access to posterior part of the septum. Synechiae formation is a common complication of this procedure. The incidence of adhesions rises particularly in cases of submucosal flap tears which is sometimes unavoidable during spurectomy. Various procedures like septal splints, nasal packings have been tried to reduce the incidence of adhesions. Recently mitomycin-C is being tried to decrease post operative adhesions after Functional Endoscopic Sinus Surgery, endoscopic Dacrocystorhinostomy, with varying degree of success. Mitomycin-C has got anti fibroblastic activity, which inhibits the fibroblasts without hampering epithelization. Eighty (80) Patients undergoing septoplasty and spurectomy were observed for any submucosal flap tear, and those developing flap tear were included in the study. The patients were divided into 2 groups of 40 each. In group-1 topical mitomycin (0.4 mg/ml) was applied at the raw area for 5 min, similarly normal saline was applied in group-2 (control).The aim of study was to evaluate the role of mitomycin-C in preventing post operative adhesions in Endoscopic septoplasty. Adhesion rate was calculated at 1 month, and compared using Chi square test. P value < 0.05 was considered significant. The adhesion rate at 1 month was 17.5% in group-1 and 45% in group-2 (P = 0.008). Incidence of adhesion decreased significantly in mitomycin-C treated group. Mitomycin-C can routinely be used in septoplasty to prevent post op adhesions, particularly in cases of submucosal flap tears/concurrent turbinate reduction procedures.

Giant Primary Sinonasal Mucosal Melanoma: A Rare Malignancy.

It is extremely rare to find a case of primary sinonasal mucosal melanoma, which is more aggressive and have poorer outcome than its cutaneous counterpart. This tumour is refractory to the treatment which includes wide surgical excision with or without adjuvant postoperative radiotherapy. We are reporting a case of 60 year old female who presented with right sided nasal mass and facial deformity, in whom the diagnosis of mucosal melanoma was made on histopathological examination and confirmed by immunohistochemistry.

Unusual Presentation of Hydatidosis - Neck Lump Causing Costo-Vertebral Erosion.

INTRODUCTION: Hydatid disease caused by larval stage of Echinococcus has been recognized endemically in many countries. Liver and lungs are the most commonly affected organs. Involvement of the head and neck region is rare and bony erosion due to hydatidosis is even rarer. CASE REPORT: We report a case of a 17-year-old girl from a poor socio-economic background who presented with a right sided supraclavicular lump, which after surgical excision and histopathological examination was diagnosed as hydatid cyst of neck. CONCLUSION: Because of its rarity in the neck region, primary diagnosis of hydatid cyst is overlooked and usually not included in the differential diagnosis of cystic neck swellings. A high index of suspicion is necessary to diagnose hydatid disease in an unusual location even in endemic areas.

Characterization of water treatment sludge and its reuse as coagulant.

Coagulation-flocculation process results in the generation of large volume of waste or residue, known as water treatment sludge (WTS), in the purification of surface water for potable supplies. Sustainable management of the inevitable waste requires careful attention from the plant operators and sludge managers. In this study, WTS produced with the optimum alum dose of 30 ml/L at the laboratory scale has been treated with sulphuric acid to bring forth a product known as sludge reagent product (SRP). The performance of SRP is evaluated for its efficiency in removing the colloidal suspensions from the Yamuna river water over wide pH range of 2-13. 1% sludge acidified with sulphuric acid of normality 2.5 at the rate of 0.05 ml/ml sludge has been observed as the optimum condition for preparing SRP from WTS. The percentage turbidity removal is greater at higher pH value and increases with increasing the dosage of SRP. The optimum SRP dosage of 8 ml/L in the pH range of 6-8 performed well in removing the colloidal suspension and other impurities from the Yamuna water. The quality of treated water met the prescribed standards for most of the quality parameters. Thus, SRP has the potential to substitute the conventional coagulants partially or completely in the water treatment process, depending on the quality needed at the users end.

Structure-Activity Relationship of Chlorotoxin-Like Peptides.

Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na⁺, K⁺, Ca⁺, Cl(-), etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity.

Facial Palsy due to Parotid Abscess: An Unusual Complication.

Facial nerve palsy is usually associated with a malignant parotid neoplasm; it is highly unusual for it to result from a benign situation, such as inflammation or infection of the parotid gland. Surgery along with prompt medical treatment is the mainstay, and in the majority of the patients, nerve paralysis recovers in the follow-up period. We report a case of a 50-year-old non-diabetic non-hypertensive female who presented with odynophagia, left-sided parotid swelling, and left facial nerve palsy. The diagnosis of facial nerve palsy due to a parotid abscess extending to the parapharyngeal space was made. Facial palsy fully recovered within 2 months.

A Study of the Use of Laryngeal Mask Airway (LMA) in Children and its Comparison with Endotracheal Intubation.

SUMMARY: Laryngeal mask airway (LMA) is increasingly being used in children as it is less invasive compared to endotracheal intubation and causes less discomfort in the postoperative period. However, some concerns remained about its safety during positive pressure ventilation in children. In a prospective randomized trial, 100 ASA I and II children weighing between 10-20 kg in the range of 2-10 years of age, scheduled for elective surgery were randomly allocated to one of the two groups of 50 patients each. The efficacy of LMA in children during positive pressure ventilation, its haemodynamic changes and postoperative complications were compared to endotracheal intubation. Insertion of LMA was easier in 94% patients while endotracheal intubation was done easily in 53% of patients only (p<0.05). The changes in haemodynamic parameters were significantly higher after endotracheal intubation as compared to LMA placement. Furthermore these changes persisted for longer duration after endotracheal intubation in comparison to LMA insertion (5 min vs 3 min). Incidence of postoperative complications i.e. bronchospasm, laryngospasm and soft tissue trauma was significantly higher (p<0.05) after endotracheal intubation as compared to LMA insertion. To conclude, the laryngeal mask airway is a suitable alternative to endotracheal intubation for positive pressure ventilation in children.

Structure-activity relationship of an alpha-toxin Bs-Tx28 from scorpion (Buthus sindicus) venom suggests a new alpha-toxin subfamily.

Scorpion venoms are among the most widely known source of peptidyl neurotoxins used for callipering different ion channels, e.g., for Na(+), K(+), Ca(+) or Cl(-). An alpha-toxin (Bs-Tx28) has been purified from the venom of scorpion Buthus sindicus, a common yellow scorpion of Sindh, Pakistan. The primary structure of Bs-Tx28 was established using a combination of MALDI-TOF-MS, LC-ESI-MS, and automated Edman degradation analysis. Bs-Tx28 consists of 65 amino acid residues (7274.3+/-2Da), including eight cysteine residues, and shows very high sequence identity (82-94%) with other long-chain alpha-neurotoxins, active against receptor site-3 of mammalian (e.g., Lqq-IV and Lqh-IV from scorpions Leiurus sp.) and insect (e.g., BJalpha-IT and Od-1 from Buthotus judaicus and Odonthobuthus doriae, respectively) voltage-gated Na(+) channels. Multiple sequence alignment and phylogenetic analysis of Bs-Tx28 with other known alpha- and alpha-like toxins suggests the presence of a new and separate subfamily of scorpion alpha-toxins. Bs-Tx28 which is weakly active in both, mammals and insects (LD(50) 0.088 and 14.3microg/g, respectively), shows strong induction of the rat afferent nerve discharge in a dose-dependent fashion (EC(50)=0.01microg/mL) which was completely abolished in the presence of tetrodotoxin suggesting the binding of Bs-Tx28 to the TTX-sensitive Na(+)-channel. Three-dimensional structural features of Bs-Tx28, established by homology modeling, were compared with other known classical alpha-mammal (AaH-II), alpha-insect (Lqh-alphaIT), and alpha-like (BmK-M4) toxins and revealed subtle variations in the Nt-, Core-, and RT-CT-domains (functional domains) which constitute a "necklace-like" structure differing significantly in all alpha-toxin subfamilies. On the other hand, a high level of conservation has been observed in the conserved hydrophobic surface with the only substitution of W43 (Y43/42) and an additional hydrophobic character at position F40 (L40/A/V/G39), as compared to the other mentioned alpha-toxins. Despite major differences within the primary structure and activities of Bs-Tx28, it shares a common structural and functional motif (e.g., transRT-farCT) within the RT-CT domain which is characteristic of scorpion alpha-mammal toxins.