Blue dye single labelling for colorimetric sentinel lymph node mapping in early endometrial cancer: A feasibility study.

Background: Surgical staging in endometrial cancer includes a systematic lymphadenectomy with significant morbidity, although its therapeutic role is unclear. Sentinel lymph node (SLN) study is a less morbid alternative to identify nodes most likely to be metastatic, permitting selective removal and thus reducing morbidity without compromising oncological safety. This study was done using blue dye single labelling to study the feasibility and utility in identifying SLN in early disease. Methods: Twenty-two patients of early-stage low-risk disease during surgical staging underwent cervical injection of methylene blue, SLN mapping, and sampling as per the standard algorithm, followed by a systematic lymphadenectomy in all cases. SLN were submitted separately for ultrastaging (US). Results: Twenty patients underwent the procedure, and SLN could be identified in 18 patients with an overall mapping rate of 90% with a bilateral mapping rate of 70%, and a negative mapping rate of 10%. 57 SLN were identified along with two suspicious non-sentinel nodes and 11 were metastatic on US with a sensitivity of 66.7% and NPV of 87.5%. All patients with metastatic nodes, however, could be identified by applying the standard SLN algorithm for sampling. Conclusion: SLN mapping algorithm with blue dye single labelling in early endometrial cancer, by identifying LN most likely to be metastatic enabling their selective removal may help avoid routine lymphadenectomies without compromising oncological safety. The procedure is simple and can be practiced at all centres and can also aid pathologists by pinpointing the likely metastatic nodes after a selective or complete lymphadenectomy.

Comparing physicians and experienced advanced practice practitioners on the interpretation of electrocardiograms in the emergency department.

BACKGROUND: Many patients present to emergency departments (ED) in U.S. for evaluation of acute coronary syndrome, and a rapid electrocardiogram (ECG) and interpretation are imperative for initial triage. A growing number of advanced practice practitioners (APP) (e.g. physician assistants, nurse practitioners) are assisting patient care in the ED. PURPOSE: This study aims to compare the interpretation of ECGs by experienced APPs, each having 10 or more years of experience, with resident physicians and attending physicians. PATIENTS AND METHODS: 99 ED providers were stratified into attendings, residents at varying levels, and APPs were tested to interpret 36 ECGs from a database of ECGs initially interpreted to be ST elevation myocardial infarctions, of which 24 were determined to have a culprit lesion by coronary intervention. RESULTS: Attending physicians were the most sensitive (0.86, 95% CI of 0.80 to 0.92) and specific (0.69, 95% Cl of 0.60 to 0.79) at interpreting ECGs, but APPs and physicians in their first year of practice out of residency were almost equally as sensitive [(0.82, 95% CI of 0.76 to 0.88) and (0.82, 95% CI of 0.76 to 0.88)] and specific [(0.62, 95% cl of 0.52 to 0.73) and (0.65, 95% Cl of 0.56 to 0.75)]. CONCLUSION: This study suggests the possibility of changing ED workflow where experienced APPs can be responsible for initial screening of an ECG, thus allowing fewer interruptions for ED physicians.

Pre-surgical staging in endometrial cancer: An opportunity for risk stratification and triage?

BACKGROUND: Endometrial cancer (EC) is treated by comprehensive surgical staging that includes a systematic lymphadenectomy. The low rates of lymph node metastasis (LNM) in early stages question the benefit of routine lymphadenectomy in low-risk disease, but the absence of a reliable method to identify these patients in whom lymphadenectomy could be omitted makes complete staging the standard of care. This study evaluated a method of preoperative staging in EC to identify patients at low risk of LNM and adjuvant treatment. METHODS: This prospective observational study compared the presurgical staging and risk triage based on endometrial biopsy (EB) and imaging (magnetic resonance imaging [MRI], Positron Emission Tomography [PET] scan) in 94 cases of EC with the final surgicopathological staging and evaluated the role of each modality in presurgical evaluation and triage. RESULTS: Ninety-four cases were triaged into 42 low-risk and 52 non-low-risk cases preoperatively. EB showed a sensitivity, specificity, and accuracy of 51.55%, 89.83%, and 75.53%, respectively, in identifying high-risk grade and histology. MRI was effective for local staging and identified tumor size, myometrial invasion, and cervical involvement with accuracy ranging from 82.20% to 97.78% for these parameters. MRI detected LNM with an accuracy of 85.11%, whereas PET exhibited an accuracy of 86.17%. The combined presurgical staging could identify low-risk disease with a sensitivity, specificity, and accuracy of 85.37%, 86.79%, and 86.17%, respectively. CONCLUSION: Preoperative staging may triage patients into low-risk and non-low-risk cases, thereby facilitating a conscious decision to omit lymphadenectomy in low-risk cases, thus avoiding unnecessary morbidity without compromising oncological safety.

IN0523 (Urs-12-ene-3α,24ß-diol) a plant based derivative of boswellic acid protect Cisplatin induced urogenital toxicity.

The limiting factor for the use of Cisplatin in the treatment of different type of cancers is its toxicity and more specifically urogenital toxicity. Oxidative stress is a well-known phenomenon associated with Cisplatin toxicity. However, in Cisplatin treated group, abnormal animal behavior, decreased body weight, cellular and sub-cellular changes in the kidney and sperm abnormality were observed. Our investigation revealed that Cisplatin when administered in combination with a natural product derivative (Urs-12-ene-3α,24ß-diol, labeled as IN0523) resulted in significant restoration of body weight and protection against the pathological alteration caused by Cisplatin to kidney and testis. Sperm count and motility were significantly restored near to normal. Cisplatin caused depletion of defense system i.e. glutathione peroxidase, catalase and superoxide dismutase, which were restored close to normal by treatment of IN0523. Reduction in excessive lipid peroxidation induced by Cisplatin was also found by treatment with IN0523. The result suggests that IN0523 is a potential candidate for ameliorating Cisplatin induced toxicity in the kidney and testes at a dose of 100mg/kg p.o. via inhibiting the oxidative stress/redox status imbalance and may be improving the efflux mechanism.

Clinico-Pathological Characteristics, Management, and Prognostic Factors of Patients with Uterine Carcinosarcoma: a Retrospective Analysis.

Uterine carcinosarcoma is a rare, highly aggressive, rapidly progressing neoplasm associated with a poor prognosis. It comprises 1-5% of all uterine malignancies but accounts for 16.4% of all deaths caused by uterine malignancies. There is a definite paucity of data available from the Indian subcontinent. Hence, we retrospectively conducted this study to analyze the clinical and pathological characteristics and outcomes of women with uterine carcinosarcoma in the past 10 years managed at the tertiary care center. This is a retrospective study of women with histologically proven uterine carcinosarcoma treated at a tertiary cancer center in South India between August 2009 and April 2019. Inpatient and outpatient records were reviewed; clinicopathological data were collected; and follow-up and survival data were ascertained. Over a period of 10 years, 20 patients were diagnosed with uterine carcinosarcoma. The majority of patients were postmenopausal (80%). Post-menopausal bleeding was the main presenting complaint in about 80% of patients. More than two-thirds of patients presented in the early stage (stage I, 55%; stage II, 20%). All patients underwent staging laparotomy. Patients with good performance status (85%) received adjuvant concurrent chemoradiotherapy and chemotherapy. At a median follow-up of 40 months, 7 (35%) patients were alive, out of which 6 are disease-free and 1 had a recurrence. The event-free survival at a median follow-up of 40 months was 40% and the overall survival was 48.5%. The outcome did not significantly differ based on the age, tumor histology (heterologous versus homologous), stage, and depth of myometrial invasion. Uterine carcinosarcoma, though rare, needs to be recognized as a distinct entity, and treated aggressively. Surgery is the cornerstone of therapy. Adjuvant concurrent chemoradiation and chemotherapy improve local control and may delay recurrence, but have shown little survival advantage. The optimal adjuvant treatment for this uncommon disease is yet to be established, highlighting the need for larger multicentric studies on this tumor.

Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa community acquired pneumonia: Prevalence and locally derived risk factors in a single hospital system.

Objectives: Current American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) community-acquired pneumonia (CAP) guidelines expand the CAP definition to include infections occurring in patients with recent health care exposure. The guidelines now recommend that hospital systems determine their own local prevalence and predictors of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) among patients satisfying this new broader CAP definition. We sought to carry out these recommendations in our system, focusing on the emergency department, where CAP diagnosis and initial empiric antibiotic selection usually ooccur. Methods: We performed a retrospective cohort study of patients admitted with CAP through any of 3 EDs in our hospital system in Northern California between November 2019 and October 2021. Inclusion criteria included an ED admission diagnosis of pneumonia or sepsis, fever or hypothermia, leukocytosis or leukopenia, and consistent chest imaging result. SARS-CoV-2-positive cases were excluded. We abstracted variables historically associated with P. aeruginosa and MRSA. Outcome measures were prevalence of P. aeruginosa and MRSA in the overall clinically defined cohort and among microbiologically confirmed cases and predictors of P. aeruginosa or MRSA isolation, as determined by univariate logistic regression, bootstrapped least absolute shrinkage and selection operator, and random forest analyses. Additionally, we describe the iterative process used and challenges encountered in carrying out the new ATS/IDSA guideline recommendations. Results: There were 1133 unique patients who satisfied our definition of clinically defined CAP, of whom 109 (9.6%) had a bacterial pathogen isolated. There were 24 P. aeruginosa isolates and 11 MRSA isolates in 33 patients. Thus, the prevalence P. aeruginosa and MRSA was 2.9% in the overall CAP cohort, but 30.3% in the microbiologically confirmed cohort. The most important predictors of either P. aeruginosa or MRSA isolation were tracheostomy (odds ratio [OR] 22.08; 95% confidence interval [CI] 10.39-46.96) and gastrostomy tube (OR 14.7; 95% CI 7.14-30.26). Challenges included determining the suspected infection type in patients admitted simply for "sepsis"; interpreting dictated radiology reports; determining functional status, presence of indwelling lines and tubes, and long-term care facility residence from the electronic health record; and correctly attributing culture results to pneumonia. Conclusion: Prevalence of MRSA and P. aeruginosa was low among patients admitted in our medical system with CAP - now broadly defined - but high among those with a microbiologically confirmed bacterial etiology. Our locally derived predictors of MRSA and P. aeruginosa can be used to aid our emergency physicians in empiric antibiotic selection for CAP. Findings from this project might inform efforts at other institutions.

Spray dried tigecycline dry powder aerosols for the treatment of Nontuberculous mycobacterial pulmonary infections.

Nontuberculous mycobacterial (NTM) pulmonary infections are a global health concern and a significant contributor to lung disease. Systemic therapies of a cocktail of antibiotics administered over a long period often lead to adverse reactions and/or treatment failure. NTM pathogens, such as Mycobacterium abscessus (Mabs), are notoriously difficult to treat due to resistance to many traditional antibiotics. However, the antibiotic tigecycline has demonstrated efficacy in vitro and in vivo against Mabs strains varying in drug susceptibility. Tigecycline exhibits instability in aqueous medium, posing delivery challenges, and has caused severe adverse gastrointestinal effects following intravenous administration, requiring treatment discontinuation. To mitigate both of these concerns, inhalation therapies using dry powder aerosols are proposed as an alternative administration route and means of delivery. Tigecycline dry powder formulations were prepared, characterized, and optimized to develop a therapeutic aerosol with low moisture, high dispersibility, and a large fraction of particles in the respirable size range (1-5 µm). The addition of lactose, leucine, and phosphate buffer salts was investigated to achieve additional stability, dispersibility, and tolerability. Preliminary delivery of the dry powders to Mabs-infected mice for 30 min per day over 7 d demonstrated a 0.91-log (87.7%) decrease in lung bacterial burden.

Phase II Trial on the Feasibility of Single-Dose Intraoperative Intraperitoneal Carboplatin in Advanced Epithelial Ovarian Cancer Following Optimal Cytoreductive Surgery.

To evaluate the feasibility administering single-dose intraoperative intraperitoneal carboplatin (IP) in advanced epithelial ovarian cancer (EOC) after optimal primary or interval debulking surgery. A phase II non-randomized prospective study conducted at a regional cancer institute from January 2015 to December 2019. The advanced high-grade epithelial ovarian cancer FIGO stage IIIB-IVA was included. A total of 86 consented patients with optimal primary and interval cytoreductive surgeries received single-dose intraoperative IP carboplatin. The immediate (< 6 h), early (6-48 h), and late (48 h-21 days) perioperative complications were recorded and analyzed. The severity of adverse events was graded on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). A total of 86 patients received single-dose intra-operative IP carboplatin during the study period. The 12 (14%) patients underwent primary debulking surgery and 74(86%) interval debulking surgery (IDS). The 13 (15.1%) patients underwent laparoscopic/robotic IDS. All the patients tolerated the intraperitoneal carboplatin well with no or minimal adverse events. Three cases (3.5%) needed resuturing for the burst abdomen, three cases (3.5%) had paralytic ileus for 3-4 days, one case (1.2%) underwent re-explorative laparotomy for hemorrhage, and one case (1.2%) mortality due to due late sepsis. The 84 (97.7%) of 86 cases received scheduled IV chemotherapy on time. Single-dose intraoperative IP carboplatin is a feasible procedure with no or minimal manageable morbidity. The procedure is user friendly combining the prognostic benefits of IP chemotherapy with assurance of earliest timely administration of chemotherapy in advanced EOC. Our study is a hypothesis generating for the future clinical trials comparing single-dose NIPEC versus HIPEC in advanced EOC.

Piperine analog PGP-41 treatment overcomes paclitaxel resistance in NCI/ADR-RES ovarian cells by inhibition of MDR1.

Chemoresistance is one of the leading causes of the failure of chemotherapy. Overexpression of P-glycoprotein (P-gp) in cancer cells is one of the most important contributing factors toward the development of chemoresistance. This study was designed to synthesize the derivatives of dihydronaphthyl and to evaluate the P-gp inhibition activity of these compounds. Among all the compounds, PGP-41 showed the most potent P-gp inhibition activity in colorectal adenocarcinoma LS-180 cells. This compound showed potent P-gp inhibition activity in chemoresistant ovarian cell line NCI/ADR-RES. Paclitaxel is one of the first lines of drugs for treating ovarian cancer and is a substrate of P-gp; therefore, NCI/ADR-RES cells are highly resistant to treatment with paclitaxel. Based on this information, we evaluated PGP-41 to overcome the paclitaxel resistance of NCI/ADR-RES cells. PGP-41 was able to sensitize the NCI/ADR-RES cells to the treatment of paclitaxel, which was evident by the reduced IC50 value of paclitaxel from 6.64 µM to 0.12 µM. The sensitization of NCI/ADR-RES cells by PGP-41 was comparable to that of elacridar and Zosuquidar. Further studies revealed that the PGP-41 exerts its effect by downregulating the expression of P-gp. Reduction of P-gp activity leads to the accumulation of higher intracellular concentration of paclitaxel, and thus allowing it to interact with its targets, which further helps in its increased efficacy. Paclitaxel was able to arrest the sensitized NCI/ADR-RES cells into G2M phase, which ultimately led to the induction of apoptotic proteins and the death of cancer cells. Being a different scaffold from zosuquidar and elacridar, further studies are required to develop PGP-41 into a potential drug to overcome chemoresistance in cancer cells.

A phase IV observational multi-centre, open-label study on efficacy and safety of tolperisone 150 mg in patients with painful muscle spasm associated with degenerative or inflammatory diseases of the musculoskeletal system.

AIMS: To generate real world clinical data on efficacy and tolerability of tolperisone 150 mg in painful muscle spasms in Indian population. SETTINGS AND DESIGN: Prospective, open-labelled, non-comparative, multi-centre observational, Post Marketing surveillance study conducted at 174 participating orthopaedic care centres across India METHODS AND MATERIAL: Nine hundred and twenty adult patients having painful muscle spasm associated with degenerative or inflammatory conditions were enrolled who received tolperisone 150 mg thrice daily orally for 7 days. Assessment of primary efficacy (muscle spasm) was done by (0-3) Likert scale. Adverse events were monitored for safety and global efficacy assessment was done by clinicians and patients at the end of study period. RESULTS: Significant improvements from baseline (p < 0.0001) in scores for muscle tone, mobility & pain were seen on days 3 & 7. At the end of study there was a significant reduction in scores by more than 80% from baseline. A subgroup analysis revealed no statistical difference in the scores in patients receiving Non-Steroidal AntiInflammatory Drug (NSAID) as compared to those receiving Tolperisone alone suggesting that Tolperisone alone could be offered to patients with painful muscle spasm who are intolerant to NSAIDs or in whom NSAIDs are contraindicated. Tolperisone was well tolerated with no sedation reported by any patient during study period. The incidence of common adverse effects like nausea, gastric irritation was less than 2%. CONCLUSIONS: Tolperisone is a safe, effective and non sedative alternative in management of acute painful spasm conditions associated with degenerative or inflammatory diseases of the musculoskeletal system. Key Messages: Tolperisone is a skeletal muscle relaxant without concomitant sedation or withdrawal phenomena. In this open-labelled, non-comparative, prospective study tolperisone was proved to be a safe & effective alternative to skeletal muscle relaxants in the management of acute painful spasm conditions associated with degenerative or inflammatory diseases of the musculoskeletal system.

Safety, Tolerability, and Pharmacokinetics of a Novel Mitochondrial Modulator, TRC150094, in Overweight and Obese Subjects: A Randomized Phase-I Clinical Trial.

TRC150094, a novel mitochondrial modulator, can restore metabolic flexibility by improving insulin resistance in preclinical studies. This study primarily aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of oral TRC150094 after conducting two double-blind, randomized, Phase-I studies, single ascending dose (SAD) and multiple ascending dose (MAD), with n = 46, in overweight/obese adult and elderly subjects. In addition, the effect of TRC150094 on pharmacodynamic (PD) efficacy markers was evaluated. PK assessments, including maximum concentration (Cmax), area under the plasma concentration (AUC), time to Cmax (Tmax), and elimination half-life (t½), were assessed at pre-specified time points. PD assessments included apolipoprotein B (ApoB), triglycerides, hepatic fat by magnetic resonance spectroscopy (MRS) and cardiopulmonary exercise testing (CPET) parameters. TRC150094 was rapidly absorbed, and the AUC of TRC150094 increased in a dose-dependent manner across all doses in non-elderly and elderly cohorts. Cmax was more than the dose-proportional for all doses in all cohorts. Tmax ranged from 0.25 to 4 h, and t½ ranged from 15 to 18 h, making TRC150094 suitable for once-daily dosing. Food did not interfere with the overall absorption of the drug. The metabolites of TRC150094 were glucuronide and sulfate conjugates, and 20% of the drug was excreted unchanged in the urine. TRC150094 at 50 mg showed an improving trend in triglycerides. A significant reduction in Apo B was observed after 50 mg dose (-2.34 vs. 13.24%, p = 0.008), which was, however, not the case after 150 mg (8.78 vs. 13.24%, p = 0.1221). Other parameters such as hepatic fat and insulin sensitivity indices (HOMA-IR, MATSUDA Index derived from OGTT) showed an improving trend for the dose of 50 mg. In terms of safety, all the AEs reported were mild to moderate in severity. None of the adverse events was considered definitely or probably related to treatment, and there were no abnormal laboratory findings. In conclusion, the PK of TRC150094 was linear with no clinically significant food effect. TRC150094 and its metabolites suggest a lesser likelihood of drug-drug interactions. Overall, TRC150094 ensured safety and exhibited suitability for all subjects. Clinical Trial Registration: EUDRA CT: 2009-014941-10 (SAD) and CTR-India registration: CTRI/2009/091/000601 (MAD).

Growing Teratoma Syndrome a Rare Clinical Entity: Two Decades Management Experience from the Regional Cancer Institute.

To study the clinical, biochemical, radiological, pathological characteristics, surgical treatment details, and follow-up of growing teratoma syndrome (GTS) patients. This is a retrospective study of GTS treated in the Department of Gynaecological Oncology at a regional cancer institute from March 2000 to March 2020. A total of 303 cases of germ cell ovarian cancers were treated, and 8 (2.6%) of 303 cases recurred as GTS during this period. The patients presenting with recurrent GTS were studied for clinical, radiological, tumor markers, surgical management, histopathology, and post-operative follow-up details that were analyzed retrospectively. The Kaplan-Meier curve was used for the survival analysis. The 8 out of 303 cases of germ cell ovarian cancers recurred as GTS and the incidence rate is 2.6% during this period. In the six (75%) of eight cases, the histopathology report was immature teratoma ovaries. The five cases (62.5%) were in advanced stage. All the eight recurrent GTS cases received optimal surgical cytoreduction. The overall disease-free survival is 85.7% and one patient has recurrence after the surgery for GTS at 23rd month of follow-up visit. All the patients are alive till date. The GTS represents a rare clinical and pathological phenomenon. Nevertheless, GTS should be considered as one of the differential diagnosis in young patients having normal tumor markers with recurrent carcinomatosis following the primary treatment germ cell tumors of ovaries. The optimal cytoreduction of recurrent GTS leads to prolonged survival and possible cure in young patients.

MiTF links Erk1/2 kinase and p21 CIP1/WAF1 activation after UVC radiation in normal human melanocytes and melanoma cells.

As a survival factor for melanocytes lineage cells, MiTF plays multiple roles in development and melanomagenesis. What role MiTF plays in the DNA damage response is currently unknown. In this report we observed that MiTF was phosphorylated at serine 73 after UVC radiation, which was followed by proteasome-mediated degradation. Unlike after c-Kit stimulation, inhibiting p90RSK-1 did not abolish the band shift of MiTF protein, nor did it abolish the UVC-mediated MiTF degradation, suggesting that phosphorylation on serine 73 by Erk1/2 is a key event after UVC. Furthermore, the MiTF-S73A mutant (Serine 73 changed to Alanine via site-directed mutagenesis) was unable to degrade and was continuously expressed after UVC exposure. Compared to A375 melanoma cells expressing wild-type MiTF (MiTF-WT), cells expressing MiTF-S73A mutant showed less p21 WAF1/CIP1 accumulation and a delayed p21 WAF1/CIP1 recovery after UVC. Consequently, cells expressing MiTF-WT showed a temporary G1 arrest after UVC, but cells expressing MiTF-S73A mutant or lack of MiTF expression did not. Finally, cell lines with high levels of MiTF expression showed higher resistance to UVC-induced cell death than those with low-level MiTF. These data suggest that MiTF mediates a survival signal linking Erk1/2 activation and p21 WAF1/CIP1 regulation via phosphorylation on serine 73, which facilitates cell cycle arrest. In addition, our data also showed that exposure to different wavelengths of UV light elicited different signal pathways involving MiTF.

Olmesartan medoxomil evaluated for safety and efficacy in Indian patients with essential hypertension: a real world observational postmarketing surveillance.

OBJECTIVE(S): To assess the efficacy and safety of once daily olmesartan medoxomil 20 mg in Indian patients with stage 1 essential hypertension. METHOD(S): This was an open label, multicentre, real world observational postmarketing surveillance conducted in male and female patients (N=825), in age group of 18 to 65 yrs who had clinically diagnosed stage 1 hypertension (JNC-7 guidelines) and were prescribed olmesartan medoxomil 20 mg once daily as treatment. There were total of seven study visits, Visit-1 (day 1) and end of study visit-7 (end of week 8). Except for those patients who did not achieve the target BP levels, all the patients continued to receive olmesartan medoxomil 20 mg for 8 weeks, given once a day at 24 hourly intervals. At end of surveillance (EOS; week 8) visit-7 clinical response to treatment was determined by "responder rate" and changes in level of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Responder rate criteria was defined as, SBP and DBP levels of <140 mmHg and <90 mmHg respectively, and for hypertensive patients with diabetes mellitus SBP and DBP levels of < 130 mmHg and < 80 mmHg respectively. RESULT(S): There were significant changes in mean sitting systolic and diastolic blood pressure, the primary end point of the study. From baseline visit to the end of the surveillance visit-7 (week 8), a mean change of -18.7 (147.86 to 129.16; p < .0001; 95% CI) in sitting SBP and a mean change of -14.47 (95.99 to 81.56; p < .0001; 95% CI) in sitting DBP respectively was observed with olmesartan 20 mg once daily. The response rate at the end of study was 81.82% and 70.18% for SBP and DBP respectively, in stage 1 hypertensive patients without diabetes mellitus. It was 73.38% and 65.47% respectively for SBP and DBP in patients with diabetes. Overall efficacy of Olmesartan medoxomil 20 mg was excellent to very good in 92.5% patients, only 05 (0.6%) of patients, reported of poor efficacy. Tolerability as assessed globally was reported to be excellent to very good by 92.1% of patient, with only one patient (0.1%) reported it to be poor. The most common adverse events reported were dizziness (82.52%), headache (63%), respiratory tract infection (50.40%) and nausea (40.24%); all the AE's were mild-moderate in nature which did not require stoppage of treatment. CONCLUSION(S): Our findings reiterated that Olmesartan medoxomil 20 mg once daily is not only effective in achieving the desired BP in a significant number of patients, it also shows excellent tolerability and hence compliance. Olmesartan is a valuable option for treatment of essential hypertension in adult Indian patients.

Anti-inflammatory and analgesic potential of OA-DHZ; a novel semisynthetic derivative of dehydrozingerone.

Despite various advances in the arena of the current system of medicine, there are numerous side effects associated with the therapeutics which essentially demand research on the development of safer therapeutics. One way is to explore the bioactive plant secondary metabolites and their semisynthetic derivatives. In context to this, we analyzed OA-DHZ, a dehydrozingerone derivative as the later has been reported to show anti-inflammatory and analgesic properties. OA-DHZ was found to be having promising anti-inflammatory and analgesic potential. OA-DHZ was found to inhibit the carrageenan-induced edema and leukocyte migration, acetic acid-induced increase in vascular permeability and lipopolysaccharide-induced pro-inflammatory cytokines like TNF-α, IL-6, and IL-1ß. Meanwhile, it was also found to potentially inhibit thermally as well as chemically induced pain signifying its analgesic/nociceptive potential. Further, safety pharmacology studies using in vivo animal models for the central nervous system, gastrointestinal tract, the cardio-respiratory system suggest that optimum functioning of vital organ systems does not get altered after single oral administration. Also, the acute toxicity study revealed its nontoxic nature up to 2000 mg/kg. This study paves the way for future exploration and development of OA-DHZ based on its potent activity and nontoxic nature.

Discovery and preclinical development of IIIM-160, a Bergenia ciliata-based anti-inflammatory and anti-arthritic botanical drug candidate.

OBJECTIVE: Bergenia ciliata (Haw.) Sternb. is used in the Indian traditional system of medicine to treat various ailments including rheumatism and to heal wounds. The objective of the present study was to perform a preclinical characterization of the B. ciliata-based botanical extract IIIM-160. METHODS: IIIM-160 was chemically standardized and analyzed for heavy metal content, aflatoxins, pesticides and microbial load. The in vitro and in vivo efficacies were determined in suitable models of inflammation, arthritis and nociception. An acute oral toxicity study was performed in Swiss albino mice. A suitable oral formulation was developed and characterized. RESULTS: Bergenin was found to be the major component (9.1% w/w) of IIIM-160. The botanical lead displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6 (IL-6) and had an excellent safety-window. It showed anti-inflammatory, anti-arthritic and antinociceptive activity in animal models and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice. The gastroretentive, sustained-release capsule formulation showed sustained-release of the bergenin over the period of 24 h, resulting in improved plasma-exposure of bergenin in Sprague-Dawley rats. CONCLUSION: The dual-activity of IL-6 inhibition and antinociception marks the suitability of IIIM-160 for treating rheumatoid arthritis. This study will serve as the benchmark for further research on this botanical formulation.

Rohitukine inhibits NF-κB activation induced by LPS and other inflammatory agents.

Rohitukine (referred to as RHK) is a bioactive chromone alkaloid isolated from the leaves of plant Dysoxylum binectariferum, which has been reported to possess diverse pharmacological properties for the treatment of inflammatory bowel disease (IBD), diarrhoea and anti-lipidemic. However, the underlying mechanism by which RHK exerts its anti-inflammatory activity has not yet demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of RHK using lipopolysaccharide (LPS) - stimulated J774A.1 macrophage cells and in-vivo inflammatory models. Results demonstrated that RHK treatment could significantly decrease the LPS-induced production of nitric oxide, prostaglandin E2 (PGE2), interleukins (ILs) and tumour necrosis factor (TNF)-α in J774A.1 cells. Molecular studies revealed that RHK inhibited the activation of upstream mediator nuclear factor-κB by suppressing the phosphorylation of IκBα and p65. In in-vivo experiments showed prominent anti-inflammatory activity of RHK. Thus, RHK could be considered as a promising candidate for the treatment of inflammatory diseases.