Pharmacological blockade of HDAC6 attenuates cancer progression by inhibiting IL-1ß and modulating immunosuppressive response in OSCC.

Interleukin-1-beta (IL-1ß) one of the biomarkers for oral squamous cell carcinoma (OSCC), is upregulated in tumor-microenvironment (TME) and associated with poor patient survival. Thus, a novel modulator of IL-1ß would be of great therapeutic value for OSCC treatment. Here we report regulation of IL-1ß and TME by histone deacetylase-6 (HDAC6)-inhibitor in OSCC. We observed significant upregulation of HDAC6 in 4-nitroquniline (4-NQO)-induced OSCC in mice and 4-NQO & Lipopolysaccharide (LPS) stimulated OSCC and fibroblast cells. Tubastatin A (TSA)-attenuated the OSCC progression in mice as observed improvement in the histology over tongue and esophagus, with reduced tumor burden. TSA treatment to 4-NQO mice attenuated protein expression of HDAC6, pro-and-mature-IL-1ß and pro-and-cleaved-caspase-1 and ameliorated acetylated-tubulin. In support of our experimental work, human TCGA analysis revealed HDAC6 and IL-1ß were upregulated in the primary tumor, with different tumor stages and grades. We found TSA modulate TME, indicated by downregulation of CD11b+Gr1+-Myeloid-derived suppressor cells, CD11b+F4/80+CD206+ M2-macrophages and increase in CD11b+F4/80+MHCII+ M1-macrophages. TSA significantly reduced the gene expression of HDAC6, IL-1ß, Arginase-1 and iNOS in isolated splenic-MDSCs. FaDu-HTB-43 and NIH3T3 cells stimulated with LPS and 4-NQO exhibit higher IL-1ß levels in the supernatant. Interestingly, immunoblot analysis of the cell lysate, we observed that TSA does not alter the expression as well as activation of IL-1ß and caspase-1 but the acetylated-tubulin was found to be increased. Nocodazole pre-treatment proved that TSA inhibited the lysosomal exocytosis of IL-1ß through tubulin acetylation. In conclusion, HDAC6 inhibitors attenuated TME and cancer progression through the regulation of IL-1ß in OSCC.

APPLICATIONS OF THREE DIMENSIONAL FACIAL COMPUTED TOMOGRAPHY IN HEAD AND NECK REGION - A REVIEW. / ЗАСТОСУВАННЯ ТРИВИМІРНОЇ КОМП'ЮТЕРНОЇ ТОМОГРАФІЇ ОБЛИЧЧЯ ПРИ ВІЗУАЛІЗАЦІЇ ОБЛАСТІ ГОЛОВИ ТА ШИЇ ­ ОГЛЯД.

3D facial CT has evolved and revolutionized diagnosis leading to better management. The limitations of conventional 2D methods limit the therapeutic options related to leading to an erroneous treatment. Although 3D facial CT is expensive, its advantages outweigh the cons. They are used in surgery, prosthetic replacement, orthodontics and forensics.

Usefulness of ultrasonography guided femoral and lateral femoral cutaneous nerve blocks in providing analgesia before giving spinal anaesthesia in patients undergoing surgery for intertrochanteric fracture of femur: A randomized clinical trial.

Background and Aims: It is challenging to give the patient position for subarachnoid block (SAB) as intertrochanteric (IT) fracture of the femur produces intolerable pain. In this study, we have analyzed the usefulness of combined ultrasonography (USG)-guided femoral nerve block (FNB) and lateral femoral cutaneous nerve block (LFCNB) to reduce the fracture pain before performing SAB. Material and Methods: A prospective, randomized, comparative study was conducted on 60 American society of anesthesiologists (ASA) grade I and II patients (18-80 years) scheduled for elective IT fracture surgery. Group A (n = 30) patients received USG-guided FNB and LFCNB using 0.75% ropivacaine before SAB. Group B patients (n = 30) received SAB only. All the patients received SAB (3 mL of 0.5% bupivacaine) by an anesthesiologist blinded to the patient groups. The patients were observed for quality of patient positioning for SAB, perioperative visual analog scale (VAS) scores, time to administration of SAB, and duration of analgesia and motor blockade. Statistical analysis was done by Student's t-test and Chi-square test. Results: Baseline VAS score (T1) was similar in both the groups. Mean T2 (VAS score just before SAB) in group-A (3.2 ± 0.98) was lower compared to group-B (8.23 ± 0.7) with P < 0.0001. The quality of patient positioning in group-A was good to optimal but in group-B, it was satisfactory to not satisfactory. Group-A had longer mean duration of analgesia 804 ± 114.28 minutes with P value < 0.0001 than group-B in which it was 200 ± 28.77 min. Backache was significant in group-B with P value of 0.038 compared to group-A. Conclusion: USG-guided FNB and LFCNB can be used as an effective supplementation to SAB in patients undergoing surgery for IT fracture of the femur as it reduces fracture site pain, provides good patient positioning during SAB, and prolongs postoperative analgesia.

Torsion of an Epididymal Cyst: A Rare Finding on Scrotal Exploration for Acute Scrotum.

Torsion of epididymal cyst (EC) is an exceedingly rare cause of acute scrotum in both children and adults. We add our case as the ninth case to literature which was an 8-year-old child presented with features of acute scrotum with history of EC on conservative management. Doppler sonography showed perfused normal bilateral testes and a 4.1 × 1.7 cm septate cystic lesion of right epididymis. On scrotal exploration, we found a haemorrhagic cystic lesion attached to the upper pole of right testis and twisted for 540 degrees with normal testis and appendage. Cyst was excised, and histopathology revealed a haemorrhagic EC. Our case was peculiar due to, presenting as acute scrotum in a child of 1-10 years age group who was conservatively managed for right-sided EC and presence of 540 degrees torsion.

Omental tuberculosis (TB) is a rare disease which can mimic Gastrointestinal malignancies: A case report.

INTRODUCTION: Omental tuberculosis is a rare disease which can mimic Gastrointestinal malignancies. It should be considered as one of the differential diagnosis when the patient presents with abdominal mass with vague symptoms. Histological diagnosis is the final conclusion in these patients. PRESENTATION OF CASE: An elderly male patient who presented with epigastric pain with epigastric mass and diagnosed with omental tuberculosis as a result of USS guided tissue biopsy revealed granuloma with central caseous necrosis. The size of the mass completely resolved after completion of anti TB treatment in this patient. DISCUSSION: Presence of caseous necrosis with granulomas in histology and positive culture of tuberculosis from tissue are the definitive diagnosis for omental tuberculosis. And the response to treatment with anti TB drug supports the diagnosis. CONCLUSION: Omental TB is a rare entity which can be misdiagnosed as GI malignancies. Medical management is the treatment of choice for omental TB. Surgery is needed when complications occur in extrapulmonary TB.

Schwartz Jampel Syndrome (SJS)-One in a Million Syndrome.

Schwartz Jampel syndrome is a very rare genetically heterogenous disorder characterized by myotonia, typical facies, growth retardation and osteoarticular changes. Prevelance of this syndrome is <1 in 100000. 150 cases have been reported in medical literature so far. We hereby report this rare syndrome in neurology.

Allergic Fungal Rhinosinusitis: A Study in a Tertiary Care Hospital in India.

The study was conducted to study the occurrence and clinical presentation of allergic fungal rhinosinusitis (AFRS), characterize the same, and correlate with the microbiological profile. Clinically suspected cases of fungal rhinosinusitis (FRS) depending upon their clinical presentation, nasal endoscopy, and radiological evidences were included. Relevant clinical samples were collected and subjected to direct microscopy and culture and histopathological examination. 35 patients were diagnosed to have AFRS. The average age was 28.4 years with a range of 18-48 years. Allergic mucin was seen in all the AFRS patients but fungal hyphae were detected in only 20%. 80% of cases were positive for IgE. All the patients had nasal obstruction followed by nasal discharge (62.8%). Polyps were seen in 95% (unilateral (48.57%) and bilateral (45.71%)), deviated nasal septum was seen in 28.57%, and greenish yellow secretion was seen in 17.14%. Direct microscopy and septate hyphae were positive in 71.42% of cases. 91.4% of cases were positive by culture. 5.7% yielded mixed growth of A. flavus and A. niger. Prompt clinical suspicion with specific signs and symptoms along with timely sampling of the adequate patient specimens and the optimal and timely processing by microscopy and culture and histopathological examination is a must for early diagnosis and management.

Essential oil constituents of Illicium griffithii and its antimicrobial activity.

The essential oil of the fruit of Illicium griffithii Hook f. et Thoms. was extracted using Clevenger's apparatus. Forty-one compounds were characterized by gas chromatography-mass spectroscopy (GC-MS). 4-Methyl-6-(2-propenyl)-1,3-benzodioxole was characterized as the major constituent, followed by linalool amongst the volatile constituents. The essential oil was found to be effective against Aspergillus niger, Penicillium spp. and Saccharomyces cerevisiae and possessed considerable activity against Staphylococcus aureus and was inactive against Klebsiella pnemoniae, Pseudomonas aureginosae, Proteus vulgaris and Escherichia coli.

Subclinical hypothyroidism and autoimmune thyroiditis in pregnancy--a study in south Indian subjects.

OBJECTIVE: To analyse the prevalence of subclinical hypothyroidism among pregnant women attending Government hospitals in South India. It is also aimed to identify the prevalence of thyroid autoimmunity in euthyroid pregnant women. MATERIALS AND METHODS: Five hundred pregnant women attending two government Obstetric and Gynecology hospitals in Chennai during a period of 5 months in 2007, were studied. Excluding subjects with known thyroid diseases, 495 subjects were examined. Detailed physical examination was done and details of pregnancy were recorded. All were subjected to blood tests for Free T4, TSH and TPO antibodies. RESULTS: Subclinical hypothyroidism was detected in 2.8%, among them TPO antibodies positivity was seen in 57.1% whereas euthyroid women had significantly lower positivity (7%). No association was seen between hypothyroidism or TPO antibody positivity with gestational age or parity. Hypothyroidism diagnosed by elevated TSH value (> or = 5.0 mg/l) was significantly associated with increasing gestational age (Trend chi2 = 6.02, p = 0.014). CONCLUSIONS: Prevalence of subclinical hypothyroidism among pregnant women is fairly high among Indians and they have high rates of TPO antibody positivity. Screening for hypothyroidism has to be included as a routine screening test to improve maternal and foetal outcomes.