The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer1,2, who were germline BRCA1 and BRCA2 wild type3. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR)4, and secondary end points included event-free survival (EFS) and overall survival (OS)5. pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P > 0.9), respectively; OS was 90% and 87.2% (log-rank P = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P < 0.001), and OS was 96% and 83% (log-rank P < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 .

A Pilot, Open-Label, Proof-of-Concept Study To Evaluate the Efficacy and Safety of Asthiposhak® Tablets in Participants Suffering From Asthikshaya or Osteopenia.

Introduction Both osteoporosis and osteopenia are prevalent public health concerns worldwide and can lead to debilitating bone fractures. This study aimed to assess the efficacy of Asthiposhak® Tablets in individuals with Asthikshaya (osteopenia) by measuring changes in the bone mineral density (BMD) score before and after the intervention, specifically between visit 1 (baseline) and visit 8 (after 180 days of treatment). Methods The single-arm study involved the screening of participants for Asthikshaya (osteopenia) using baseline investigations, which included a bone mineral density (BMD) assessment through a dual-energy X-ray absorptiometry (DEXA) scan. A total of 36 participants were enrolled in the study, who took two Asthiposhak Tablets three times a day with lukewarm water, for a period of 180 days. Safety assessments, along with evaluations of BMD (DEXA Scan), Ayurvedic Symptom Score, and serum biochemical markers, were conducted through blood investigations. Efficacy and safety data were analyzed using 'intention-to-treat' analysis. Descriptive statistics were used to express data in percentages, mean ± SD, or median (IQR). Data at different intervals were compared using paired t-tests or Wilcoxon signed-rank tests. One-way analysis of variance (ANOVA) with Bonferroni correction tested the significance between visits for the Ayurvedic Symptom Score, and Friedman's two-way analysis of variance by ranks measured differences in vital parameters. The significance level used was p<0.05. Results Out of the initially recruited 36 participants, 30 successfully completed the study, consisting of 12 males and 18 females, with an age range of 40 to 70 years and a mean age of 51.33 years. After 180 days of treatment with Asthiposhak Tablets, a statistically significant (p<0.05) improvement in hip and spine BMD (T-score) was observed. Additionally, significant reductions in the mean Total Ayurvedic Symptom Score were noted at both 90 and 180 days of treatment compared to day 0. Moreover, the levels of bone-specific alkaline phosphatase and osteocalcin, serum bone markers, showed statistically significant (p<0.05) reduction after 180 days of treatment compared to day 0. Importantly, all safety variables, including laboratory investigations, remained within the normal range following the 180-day treatment with Asthiposhak Tablets. Conclusion Asthiposhak Tablets exhibited significant efficacy in enhancing both BMD (T-score) and Ayurvedic Symptom Score, thereby substantiating their osteoprotective potential in individuals with Asthikshaya (osteopenia). Furthermore, the tablets were found to reduce the levels of biochemical markers, such as serum bone-specific alkaline phosphatase and osteocalcin, suggesting their anti-resorptive action.

A Pilot, Prospective, Randomized-Controlled Study to Evaluate the Efficacy and Safety of Arsha Hita™ in the Treatment of Anal Fissures.

Introduction Anal fissures are tears in the anal canal that cause pain, bleeding, and spasms. They can be treated with non-operative options such as sitz baths, local anesthetics, topical nitrates, oral fiber, and calcium channel blockers, but some patients require surgery. Topical nitrates have side effects such as severe headaches, while topical calcium channel blockers can cause itching. There is a need to explore alternative treatments with fewer side effects. This proof-of-concept pilot study aimed to compare the efficacy and safety of a combination of Arsha Hita™ tablets and ointment (Shree Dhootapapeshwar Limited, Mumbai Maharastra, India) (test treatment) with a combination of lidocaine 1.5% w/w + nifedipine 0.3% w/w cream for local application and Isabgol powder (6 g) orally as an active comparator (standard treatment), which is the standard treatment of anal fissures as per the Association of Colon and Rectal Surgeons of India (ACRSI) guidelines. Methodology This study was a single-center, prospective, randomized-controlled study conducted in Karnataka, India. Participants were screened for anal fissures and randomized to receive either standard treatment (Group A) or test treatment (Group B) for 14 days, and were re-evaluated after two, four, and six weeks. The study assessed signs and symptoms related to anal fissures, such as pain post-defecation on Visual Analog Scale (VAS), bleeding per anus grading, wound healing grade, stool consistency, and stool frequency. Compliance, inter-current illness, and concomitant therapy were noted at each visit. The study used independent sample t-tests to compare variables at baseline and chi-square or Fisher's exact tests to compare the number/proportion of participants achieving primary and secondary endpoints. Mann-Whitney U test was used to compare median composite scores at baseline and Visit 4, and Friedman's two-way analysis of variance was used to compare median composite scores across the four visits (p < 0.05 was considered significant). Descriptive analysis was used to assess VAS, bleeding, and healing grades. Results The study included 53 participants with anal fissures, of which 25 out of 27 allocated in Group A (two drop-outs) received standard treatment, and all 26 allocated in Group B received Arsha Hita treatment. At the end of the study, 11 participants in Group B achieved a 90% reduction in composite scores compared to only three patients in Group A (p<0.05). Both groups showed improvement in pain on defecation, severity of bleeding, healing of anal fissure wound, and participant's and physician's global impression score. Group B had significantly better results in terms of VAS score, resolution of per-anal bleeding, and physician's global impression score (p<0.05). There were no adverse events in either group during the six-week treatment period. Conclusion The pilot study provides evidence that the combination of Arsha Hita tablets and Arsha Hita ointment may be more effective and safer for treating anal fissures than the standard treatment. The test treatment group experienced greater pain relief, complete resolution of per-anal bleeding, and better global impression scores than the standard treatment group. These findings suggest the need for further research through larger, randomized controlled trials to determine the efficacy and safety of Arsha Hita in treating anal fissures.

A prospective, single centre, open label, single arm pilot study to evaluate the efficacy and safety of Amlapitta Mishran Suspension in participants with endoscopic gastritis.

BACKGROUND: Endoscopic gastritis is associated with symptoms of gastritis, along with endoscopic findings. Amlapitta Mishran has multiple active components that act via various mechanisms in patients with gastritis symptoms. We planned to conduct this study to find out the efficacy and safety of Amlapitta Mishran in patients with endoscopic gastritis. OBJECTIVES: To find out efficacy of Amlapitta Mishran in patient with endoscopic gastritis. MATERIALS AND METHODS: This study was an open-label, prospective, single-center study. Thirty participants were recruited, and Amlapitta Mishran Suspension was given for 30 days. Blood investigations for safety were performed at baseline (Visit 1), on Visit 3 and Visit 4. Endoscopy was performed at baseline and Visit 4, and stomach erosion score was recorded. Amlapitta Symptom Rating Scale score, Postprandial Distress Syndrome (PPDS) score, and Epigastric Pain Syndrome (EPS) score were efficacy endpoints. RESULTS: Out of the 30 participants recruited, 28 participants completed the study. The median age of participants in the study was 26.50 years. A statistically significant (P<0.05) reduction was seen in endoscopy score at Visit 4 as compared to baseline (Visit 1) by Wilcoxon Signed Rank test. Amlapitta Symptom Rating Scale score, PPDS score, EPS score also exhibited significant reduction (P < 0.05) at Visit 3 and Visit 4 as compared to baseline by Friedman's test with post hoc analysis. No statistically significant reduction was seen in these scores from Visit 3 to Visit 4, except for the EPS score. At the end of Visit 4, 18 (64%) participants had an endoscopy score of 1 (no erosions). At the end of Visit 4, ≥ 50% improvement was seen in Amlapitta Symptom Rating Scale score in 27 (96%) participants, PPDS score improved by ≥ 50% in 25 (89%) participants, and EPS score improved by ≥ 50% in 26 (93%) participants. All safety variables including laboratory investigation were within the normal range in all visits. CONCLUSION: Amlapitta Mishran Suspension effectively reduced endoscopic gastritis scores in the participants and reduced the symptoms of gastritis measured by the Amlapitta Symptom Rating Scale, PPDS, and EPS scores with no adverse events.

Correction to: Cardioprotective effect of Hrudroga Chintamani Rasa in isoproterenol induced cardiotoxicity in male Sprague Dawley rats.

[This corrects the article DOI: 10.1007/s40200-022-01012-4.].

Cardioprotective effect of Hrudroga Chintamani Rasa in isoproterenol induced cardiotoxicity in male Sprague Dawley rats.

Purpose: Ayurvedic system, a traditional medicinal system has mentioned a preparation Bruhat Vata Chintamani Rasa (Suvarnayukta) for management of heart diseases. Hrudroga Chintamani Rasa (HCR) is a formulation containing Bruhat Vata Chintamani Rasa and a few additional ingredients having beneficial effects in heart diseases. The present study was designed to investigate the cardioprotective activity of the Hrudroga Chintamani Rasa in isoproterenol (ISO)-induced myocardial infarction in rats. Methods: Male Sprague Dawley rats were treated with HCR at a dose of 56.16 and 112.32 mg/kg for 30 days. Animals received ISO (85 mg/kg. s.c.) on 28th and 29th day at an interval of 24 h. Result: Disease control animals treated with HCR at a dose of 56.16 mg/kg and 112.32 mg/kg to rats showed a significant reduction in elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase MB (CK-MB), and prevented loss of depleted antioxidant enzymes from the cardiac tissue. ISO-altered electrocardiogram pattern and haemodynamic parameters were also brought about to normal by treatment with HCR. HCR treatment also improved the levels of 5' adenosine monophosphate-activated protein kinase (AMPK) and Silent information regulator 1 (SIRT1) which have potent role in antioxidant defence mechanism. Histopathological findings also showed HCR treatment prevented cardiac tissue from damage. Conclusion: HCR treatment showed a significant cardioprotective effect in ISO-induced cardiotoxicity in rats probably because of the potent antioxidant activity. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-022-01012-4.

Evaluation of chronic toxicological profile of herbo-mineral formulations: Shwaskas Chintamani Rasa and its marketed formulation namely Kas Shwas Hari Rasa.

BACKGROUND: Shwaskas Chintamani Rasa (SKC) and Kas Shwas Hari Rasa (KSH) are the Ayurvedic herbo-mineral formulations. These Ayurvedic formulations contain heavy metals which is the reason of concern and might bring up the safety issue. OBJECTIVE: This research article is aimed to study chronic toxicity of SKC and KSH for safety aspect in Wistar rats. MATERIAL AND METHOD: A study group of 220 healthy rats were divided into six groups. These rats were administered with SKC and KSH formulations where both the formulations were administered for 180 consecutive days. SKC was administered at doses of 58 mg/kg (equivalent to therapeutic dose i.e. TD), 145 mg/kg (2.5 TD), 290 mg/kg (5 TD) and KSH was administered at dose of 58 mg/kg (TD). According to OECD guideline 452, the effect of these formulations was examined on hematology, serum biochemistry and histopathology of various organs. RESULTS: Both the formulations did not produce any signs or symptoms of treatment related toxicity in both male and female Wistar rats at therapeutic dose (TD), 2.5 times TD and 5 times TD. CONCLUSION: Based on these findings, the NOAEL (No observed adverse effect level) for test formulations SKC and KSH tablets in male and female wistar rats concluded to be preclinically safe.

Factors associated with adjuvant systemic anti-cancer treatment discontinuation for early breast cancer during the COVID-19 pandemic.

OBJECTIVE: The Covid-19 pandemic led to challenging discussions between oncology clinicians and patients regarding additional risks posed by SARS-CoV-2 infection whilst receiving systemic anti-cancer therapies (SACT). We assess the potential factors affecting discontinuation of adjuvant early breast cancer treatment during the pandemic. METHODS: Data were collected on all patients with early breast cancer undergoing adjuvant SACT, between 16 March and 17 April 2020 at a single UK cancer centre. Univariate binary logistic regression analysis was performed on variables including age, recurrence risk, Index of Multiple Deprivation decile, presence of physical comorbidities, modality of treatment (neoadjuvant or adjuvant), type of treatment (cytotoxic chemotherapy or monoclonal antibodies), percentage of cycles completed and availability of alternative treatments, with a binary dependent variable on treatment discontinuation. RESULTS: Sixty-two patients with early breast cancer were identified: 18 receiving neoadjuvant and 44 adjuvant therapies. Median age was 57.5 years (range 31-75 years). Age (P = 0.02), percentage of treatment cycles completed (P = 0.014) and presence of alternative treatment options (P = 0.019) were significant factors for SACT discontinuation during the height of the Covid-19 pandemic. CONCLUSION: Factors affecting patients' decisions to discontinue SACT for early breast cancer during the Covid-19 pandemic were elucidated, which may help identify patients requiring additional support.

Syndiotactic hexamer peptide nanodots.

Spatial confinement of excitons in the nano-crystalline region of semiconducting nanostructures differ significantly from the optoelectronic properties exhibited by the bulk material. We report spike-like absorption observed in the UV spectrum of a phenylalanine hexamer peptide [(Ff)3-OH] nano-assembly, which may be attributed to the spatial confinement of electrons to the dimension of quantum dots. Interdependency of the UV and PLE spectrum of the peptide confirms the existence of quantum confinement in (Ff)3-OH nano-assemblies.

Anti-inflammatory activity of Atavijambira (Atalantia monophylla DC.) root and stem.

Background: Atalantia monophylla DC. family Rutaceae, a promising drug, has multifaceted ethnomedicinal claims to treat rheumatism, arthritis, paralysis, cough, skin diseases, etc., In traditional practice, root and stem are administered to treat rheumatism and arthritis, respectively. Aim: The aim of this study was to evaluate the anti-inflammatory activity of the root and stem of A. monophylla against carrageenan-induced acute paw edema in wistar albino rats. Materials and methods: Shade dried root and stem were grinded separately into a fine powder (120#) by the mechanical grinder. Test drugs were prepared in Phanta (hot infusion) form and used as fresh (A. monophylla root Phanta [AMRP] and A. monophylla stem Phanta [AMSP]). Difference between the groups was statistically determined by one-way ANOVA, followed by Dunnett's multiple "t" test for unpaired data. Results: AMSP showed a significant decrease in paw inflammation at all-time interval (P < 0.05), whereas AMRP produced nonsignificant decrease in paw inflammation at 1 h (43.53%) and 5 h (25.74%) while significant (P < 0.05) anti-inflammatory activity at 3 h (36.35%) in comparison with the normal control group. Conclusion: The present study concluded that A. monophylla stem is having significant anti-inflammatory activity in comparison to its root when administered in Phanta form against carrageenan-induced acute inflammation in rats.

Assessment of Chronic Toxicity of an Ayurvedic Herbo-Metallic Formulation Rasaraj Rasa in Wistar Rats.

Objectives: This study aimed to assess the adverse effects of Rasaraj Rasa tablets after repeated oral administration for 180 days in Wistar rats. Methods: Wistar rats were divided into five groups, of which three were treated with 54, 162, and 270 mg/kg body weight of Rasaraj Rasa, respectively, which correspond to one, three, and five times the proposed human therapeutic dose, for 180 days consecutively. The fifth group (satellite) also received 270 mg/kg body weight of Rasaraj Rasa for 180 days. Body weight and food intake were measured weekly. At the end of the study, all rats were sacrificed, and their blood, serum, and organs were collected and examined using hematology, serum biochemistry, gross pathology, and histopathology tests. In contrast, the satellite group was kept for 4 weeks after treatment. Results: No significant treatment-related toxicological findings were observed in the clinical features, body weight, laboratory findings, and pathological findings of the high-dose treated groups, when compared to those of the control group. Conclusion: The no-observed-adverse-effect-level for Rasaraj Rasa in Wistar rats is set at 270 mg/kg body weight.

A novel peptide design aids in the expression and its simplified process of manufacturing of Insulin Glargine in Pichia pastoris.

Manufacturing of insulin and its analogues relied upon in vitro enzymatic cleavages of its precursor forms (single chain precursor, SCP) at both ends of a connecting peptide (C-peptide) that links the respective B-chain and A-chains to corresponding final forms. We have demonstrated a simplified approach of cleaving P. pastoris expressed SCP, distinctly at one site for conversion to insulin glargine. The design of the precursor was made in such a way that there is no C-peptide in the precursor which needs to be removed in the final product. Instead of traditional both side cleavage of the C-peptide and removing the C-peptide (by trypsin), followed by 2nd enzyme reaction (typically carboxipeptidase B), present work established only one side cleavage of the sequence by only trypsin converts the precursor to final insulin glargine product. The novel design of the precursor helped in producing insulin glargine in a single step with an application of single enzyme brought high degree of process efficiencies. Highly purified product was generated through two reversed phase high pressure chromatographic steps. Purified product was compared with the reference product Lantus®, for various physico-chemical and biological properties. Primary, secondary and tertiary structures as well as biological pharmaco-dynamic effects were found comparable. High cell density fermentation that gave a good yield of the SCP, a single step conversion to insulin glargine, enabled by a unique design of SCP and a distinct purification approach, has led to a simplified and economical manufacturing process of this important drug used to treat diabetes. KEY POINTS: • Novel concept for processing single chain precursor of insulin glargine • Simple and economic process for insulin glargine • Physicochemical characterization and animal Pharmacodynamics show similarity to Lantus.

An experimental study to evaluate Gunasankarya (combination of properties).

Introduction: Gunasankarya implies the combination or admixture of different Guna (properties) in a Dravya (substance). Every Dravya in this world is composed of different Guna varying in their quantity and potency. The final resultant action of the Dravya depends on the combination of Guna and their interaction with each other. Aim: The present study was aimed to explain the manifestation of Karma (action) of a Dravya through its Guna (properties) and to evaluate the effect of the combination of Sheeta Guna (cool property) with different other Guna on digestion and metabolism in an animal model. Materials and methods: The test drugs Usheera (Vetiveria zizanioides Linn.) and Bala (Sida cordifolia Linn.) were dried and powdered. A total of 18 adult healthy male and female Wistar strain albino rats were grouped randomly into three groups out of which the first was the control group and administered with distilled water. The second and third groups were fed with powder of Usheera and Bala, respectively, in the suspended form in distilled water. Test drugs were administered daily for 12 consecutive days. During the experimental phase, relative food intake, relative water intake, relative urine output, relative stool output, and food conversion ratio were recorded on the 3rd, 6th, 9th, and 12th day among which the 3rd day was considered as the initial day for the assessment, whereas body weight was measured from the 1st day of the study. Throughout the study, the main focus was on how these parameters change in Usheera and Bala-treated rats which are having different combinations of Guna with reference to the control group. Results: Both Usheera and Bala groups showed a nonsignificant increase in relative food and water intake, nonsignificant increase in relative urine output, significant decrease in relative stool output, and significant increase in food conversion ratio. Body weight was nonsignificantly increased in Usheera group, whereas it was nonsignificantly decreased in Bala group. This study aimed to show how the Guna are interacting and resulting in Karma either by dominating or suppressing or giving a combined effect of Guna. This study provides initial data regarding the concept of Gunasankarya (combination of properties). Conclusion: The study concludes that all the Guna in a Dravya interact and exhibit their resultant action, i.e., Karma based on Gunasankarya, with emphasis on example of assessment of the effects of Sheeta Guna Dravya, namely, Usheera and Bala on physiological parameters (digestion and metabolism) have been assessed experimentally in animal models to evaluation of the combination of Guna.

Chronic toxicity study of Sameera Pannaga Rasa in Charle's foster albino rats.

INTRODUCTION: Sameera Pannaga Rasa (SPR) is a Kupi Pakwa Rasayana (a mercurial-arsenical formulation of Ayurveda prepared by specific pharmaceutical-controlled, indirect heat treatment [sand bath] in glass bottle) that contains Shodhita Parada (processed mercury), Shodhita Gandhaka (processed sulfur), Shodhita Haratala (processed arsenic trisulfide), Shodhita Somala (processed arsenic oxide) and Shodhita Manahshila (process arsenic disulfide) in equal quantity as ingredients. Parada, Haratala, Manahshila and Somala are highly potent minerals which are included in the Drug and Cosmetic Act 1940 under Schedule E1 because of their toxic nature in crude form. MATERIALS AND METHODS: In the present study, SPR was evaluated for safety profile through its chronic toxicity study in Charle's foster albino rats. The test drug was made into suspension in vehicle (4 ml honey and 7 ml distilled water). The test drug was administered orally once a day for 90 consecutive days in the dose of 11.25 (therapeutic dose [TED]), 56.25 (5 times TED) and 112.25 mg/kg (10 times TED). Animals were sacrificed on 91st day and animals of recovery group were sacrificed on 121st day. Parameters such as hematological, serum biochemical, and histopathology of various organs were studied. RESULTS: Test drug at a higher dose level and recovery study showed no toxic effect in albino rats during chronic toxicity study. CONCLUSION: SPR is found to have no toxic effect in albino rats during the repeated dose, oral, chronic toxicity study of 90 days, even at 10 times therapeutic equivalent dose (112.25 mg/kg) and even during recovery period of 1 month. It may be safety used at TED level.

Impact of l-carnitine on lipid content and post thaw survivability of buffalo embryos produced in vitro.

The aim of the present study was to see the impact of L-Carnitine (LC) on lipid biosynthesis and metabolism of buffalo embryos, and post thaw blastocyst survivability. In vitro fertilized (IVF) embryos were derived from slaughterhouse derived COCs and cultured in different doses of LC i.e. 0, 1 mM, 1.5 mM, 2 mM starting at 48 h post IVF. Blastocyst rate was significantly (p < 0.05) higher in 1.5 mM group than control and 1.0 mM group. Lipid content was measured indirectly by fluorescent intensity of lipid droplets after Nile red staining, and it was lower (p < 0.05) in treated than control groups. CPT1B, DGAT2 and DGAT1 mRNA expression was up regulated (p < 0.05) while AMPKg1 expression was down regulated in 1.5 mM and 2 mM groups compared to other groups (p < 0.05). mRNA expression of GLUT1, OCT4 and IFN-tau was higher (P < 0.05) in 1.5 mM group than the control group. Expression of BAX was down regulated at 1.5 mM LC. Blastocyts were vitrified by a modified OPS method and post thaw survivability of blastocysts was higher (P < 0.05) in 1.5 mM LC than other groups. In post thaw blastocysts, mRNA expression of GLUT1, OCT4 and IFN-tau was higher (P < 0.05) in 1.5 mM than other groups. Thus, it can be concluded that supplementation of l-carnitine (1.5 mM) in embryo culture media improved the quality of buffalo embryo production and post thaw blastocysts survivability by reducing fatty acid synthesis, enhancing fatty acid metabolism, and reducing lipid droplet formation.

Analgesic and anti-inflammatory activities of Bulbophyllum neilgherrense Wight. pseudobulb: A folklore plant.

BACKGROUND: Bulbophyllum neilgherrense Wight. is an epiphytic orchid used extensively by the tribes of Karnataka in various diseases such as heart disease, leukoderma, skin allergy and rheumatism. It is used both internally and as an external application. In rheumatism, pseudobulbs chopped and boiled in coconut oil are applied externally. AIM: This study aims to evaluate analgesic and anti-inflammatory activities of B. neilgherrense Wight. pseudobulb powder in experimental animals. MATERIALS AND METHODS: Shade-dried pseudobulb were pulverized into fine powder. The analgesic activity of test drug was evaluated with tail-flick response and formalin-induced paw licking and anti-inflammatory activity with carrageenan-induced paw edema and formaldehyde-induced edema in Charles Foster albino rats. Statistically, the values were assessed with one-way analysis of variance followed by Dunnett's multiple t-test and Student's t-test for paired and unpaired data. RESULTS: Administration of pseudobulb powder showed significant increase in tail-flick response at 30 min (51.75%), at 60 min (108.24%), 120 min (81.12%), and 180 min (23.84%). Test drug produced nonsignificant inhibition of carrageenan-induced paw edema at 1 h (37.25%) and 5 h (15.67%) compared to control group and did not produced any effect in formalin-induced edema. CONCLUSION: The present study concluded that the test drug has central analgesic activity against radiant heat-induced pain, moderate anti-inflammatory activity against carrageenan-induced acute inflammation.

Acute and subchronic toxicity study of Tamra Bhasma (incinerated copper) prepared with and without Amritikarana.

BACKGROUND: Tamra Bhasma (TB) is one among herbo-metallic preparations extensively used in routine ayurvedic practice. In the present era, Bhasma preparations used in ayurvedic system of medicines are always under stern observations for containing heavy metals which may raise the question of safety aspect. OBJECTIVE: In the present study, TB prepared with and without Amritikarana was subjected to toxicity study to ascertain the role of Amritikarana on safety profile of TB in rats. MATERIALS AND METHODS: Both the samples of TB were administered to rats for 28 consecutive days at the doses of 5.5, 27.5, and 55 mg/kg. The effects of both drugs were assessed on ponderal changes, hematological, serum biochemical, and histopathology of various organs. RESULTS: Results showed that both the samples of TB did not produce any sign and symptoms of toxicity at therapeutic dose level (5.5 mg/kg) and therapeutic equivalent dose (TED) × 5 (27.5 mg/kg) while at higher dose of TED × 10 (55 mg/kg) TB has mild toxicity in liver, kidney, heart, and thymus on repeated administration for 28 days in rats. The sample without Amritikarana has more magnitude of toxicity than the sample with Amritikarana. CONCLUSION: From the present study, it is concluded that TB with Amritikarana was found to be relatively safer than TB without Amritikarana at different dose levels in rats and hence suggest for safely use in humans at therapeutic dose level. It proves the role of Amritikarana in the preparation of TB.

A multicentre study of the evidence for customized margins in photon breast boost radiotherapy.

OBJECTIVE: To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT). METHODS: Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated. RESULTS: For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone. CONCLUSION: If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility. ADVANCES IN KNOWLEDGE: Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others.

Experimental evaluation of antipyretic and analgesic activities of Amalakyadi Gana: An Ayurvedic formulation.

INTRODUCTION: In Ayurvedic classics, the symptom fever is considered as a separate disease called Jwara. Acharya Sushruta has mentioned Amalakyadi Gana for treatment of all types of Jwara, which contains four drugs namely Amalaki (Emblica officinalis Gaertn.), Haritaki (Terminalia chebula Retz.), Pippali (Piper longum L.), and Chitraka (Plumbago zeylenica L.). AIMS: To evaluate the antipyretic and analgesic activity of Amalakyadi Gana in experimental animals. MATERIALS AND METHODS: Decoction and alcohol soluble extract of Amalakyadi Gana were used in the present study. Antipyretic activity of dosage forms were carried out against yeast-induced pyrexia in Wistar albino rats. Analgesic activity was evaluated using radiant heat model and formalin induced paw licking in Wistar albino rats. RESULTS: In yeast-induced pyrexia model, both dosage forms of test drug produced marked decrease in rectal temperature after 3 h, 6 h, and 9 h among which extract produced statistically significant decrease after 6 h compared to control group. In the tail flick method, both forms of test drug showed insignificant increase in tail flick response after 180 and 240 min compared to control group and in formalin induced paw liking model decoction form of test drug significantly increased the latency of onset of paw licking and decreased the paw licking in early phase while alcoholic extract produced insignificant effect compared to control group. CONCLUSION: Decoction and alcoholic extract of Amalakyadi Gana has moderate antipyretic activity in rats, which may be due to inhibition of the synthesis and/or release of local PGE2. Further, Amalakyadi Gana has mild analgesic effect through central and peripheral mechanism. The result of the present study provide further scope for development of new palatable dosage form and tested clinically for better efficacy.

Evaluation of acute toxicity and intestinal transit time of Olax scandens Roxb. leaves.

INTRODUCTION: Olax scandens Roxb. is a shrub or small tree found throughout tropical India. Fruits and leaves of this plant are used for medicinal and food purpose. Traditionally, leaves of O. scandens are used as vegetable in constipation. AIM: To evaluate the acute toxicity and intestinal transit time of O. scandens leaves on experimental animals. MATERIALS AND METHODS: Acute oral toxicity study for sample was carried out following OECD guidelines. Evaluation of intestinal transit time was carried out in the dose of 1300 mg/kg by adopting Kaolin expulsion test and latency of the onset of kaolin expulsion in fecal matter in mice. RESULTS: The results show that the test drug is not likely to produce any toxicity in higher dose. In kaolin expulsion test, the drug produced mild increase in intestinal motility in mice proved by fast clearance of kaolin pellet in comparison to control group. CONCLUSION: The leaves of O. scandens are safe at higher dose and showed mild laxative activity in the dose of 1300 mg/kg body weight of mice.