Symptoms Of Acute Toxicity Research Articles

Acute and subchronic oral toxicities of “Da day An Chau” tablets in experimental animals

In this study, the toxicities of “Da day An Chau” tablets (DDAC) were assessed on experimental animals. To evaluate the acute toxicity on Swiss mice according to World Health Organization Guidance and to determine LD50 refer to the method of Litchfield – Wilcoxon. The subchronic toxicity study of DDAC at two doses (0.58 g/kg/day and 1.74 g/kg/day) was conducted in rats for four consecutive weeks. Evaluation of general conditions and weight of rats during the study period. Rat’s blood was taken for hematological and biochemical evaluations. The livers and kidneys microscopes were evaluated at the end of the experiment. The result revealed that mice were taken up to a maximum dose of 25.71 g/kg with no symptoms of acute toxicity; LD50 of DDAC has not been determined. At two doses, the subchronic toxicity study did not change rats’ body weight, hematological, biochemical parameters, and microscopic of the livers and kidneys during the study period.

Serotonin Toxicity Versus Withdrawal: Clonidine One Size Fits All?

Serotonin discontinuation syndrome (SDS) can result in a constellation of symptoms exhibited by infants exposed to selective serotonin reuptake inhibitors or other psychotropic drugs during pregnancy. Currently, there is no consensus regarding the pharmacologic management of SDS. We report our experience with clonidine for the management of a term infant with poor neonatal adaption. The infant exhibited biphasic symptoms of acute toxicity at birth and a plateauing of symptoms, followed by subsequent withdrawal symptomatology requiring the use of clonidine in doses up to 4 mcg/kg/dose every 3 hours for control of symptoms. The 38-week gestation Caucasian male infant was born to a mother with major depressive disorder, which was managed with sertraline, trazodone, venlafaxine, and buspirone throughout her pregnancy. The infant exhibited severe hypertonia at delivery and continued to have hypertonia, tremors, hypoglycemia, and feeding issues upon admission to the NICU. The initial Modified Finnegan Neonatal Abstinence scores were extremely elevated, and clonidine was started at 1 mcg/kg/dose every 3 hours and then the dose was titrated up to 4 mcg/kg/dose. This is the first report documenting the use of clonidine to manage serotonin toxicity at birth followed by subsequent neonatal withdrawal associated with maternal antidepressant drug use during pregnancy.

The role of dietary supplements, including biotics, glutamine, polyunsaturated fatty acids and polyphenols, in reducing gastrointestinal side effects in patients undergoing pelvic radiotherapy: A systematic review and meta-analysis

Background and purposePelvic radiotherapy (RT) often results in gastrointestinal toxicity and clinical trials have demonstrated a potential benefit of dietary supplements in alleviating acute effects. However, no prophylactic agents have been approved to date for relief of gastrointestinal side-effects caused by pelvic radiation. In this systematic review, we evaluated the efficacy of dietary supplements in preventing or alleviating symptoms of gastrointestinal toxicity in patients undergoing pelvic RT. Materials and methodsCENTRAL, MEDLINE, EMBASE, and ClinicalTrials.gov were searched up to June 2020 for randomised controlled trials. Interventions included four supplement categories: biotics, glutamine, poly-unsaturated fatty acids and polyphenols. Efficacy was determined with reference to outcomes based on symptoms of acute gastrointestinal toxicity, including diarrhoea, nausea, vomiting, flatulence/bloating, bowel movement frequency, tenesmus and rectal bleeding. ResultsTwenty-three randomised controlled trials (1919 patients) were identified in this review. Compared with placebo, probiotics (RR = 0.71; 95% CI: 0.52 to 0.99), synbiotics (RR = 0.45; 95% CI: 0.28 to 0.73) and polyphenols (RR = 0.30; 95% CI: 0.13 to 0.70) were significantly associated with a lower risk of diarrhoea. Biotic supplements also reduced the risk of moderate to severe diarrhoea (RR = 0.49; 95% CI: 0.36 to 0.67) and the need for anti-diarrhoeal medication (RR = 0.64; 95%CI: 0.44 to 0.92). In contrast, glutamine had no effect on acute symptoms (RR = 1.05; 95% CI: 0.86 to 1.29). There was a non-significant trend for reduction in nausea and mean bowel movements per day using dietary supplements. ConclusionsBiotic supplements, especially probiotics and synbiotics, reduce acute symptoms of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.

Idiosyncratic Reaction to Single 7.5 mg Dose of Methotrexate

Methotrexate (MTX) is one of the most common systemic immunosuppressive agents prescribed in dermatology. MTX toxicity targets skin, gastrointestinal mucosa, kidney, liver, and bone marrow. Toxic effects of MTX presenting as hepatic, renal, pulmonary, and bone marrow disorders occur less frequently than the minor effects but may be life-threatening. Characteristic signs and symptoms of acute MTX toxicity are based on extent and severity of organ involvement. Here, we report a 55-year-old married male, known case of chronic plaque-type psoriasis presenting with reaction to single dose of tablet MTX 7.5 mg as advised by the dermatologist for his disease. On history and clinical examination, diagnosis of idiosyncratic reaction to single dose of tablet MTX 7.5 mg was made.

Acute carbamazepine toxicity in a child: A case report

Carbamazepine is a commonly prescribed antiepileptic drug with a potential to cause fatal toxicity in acute overdose in children. Symptoms of acute toxicity include central nervous system depression, seizures, anticholinergic toxidrome, and arrhythmias. We report a 5 year old male child with accidental carbamazepine toxicity treated sussessfully with good suppotrive management. Intestinal decontamination therapies may be beneficial if used at the appropriate time. Multidose activated charcoal may be used if multiple controlled release tablets are ingested. Extracorporeal therapies for drug removal may be required in life-threatening toxicity to reduce plasma drug levels and hasten recovery. Appropriate and timely management leads to excellent neurological outcome.

Occupational Pesticides Intoxication among Agricultural Workers

Background: Pesticide intoxication is a public health problem in many developing countries. Approximately 18.2 per 100 000 agricultural workers worldwide have occupational-related pesticide acute and chronic toxicity symptoms. Objective: This study aimed to investigate the toxic symptoms in pesticide-exposed agricultural workers. Patients and Method: A cross sectional study was conducted on 390 agricultural workers using an interview questionnaire that consists of socio-demographic and exposure data, safety practices and self-reported toxicity symptoms. Physical examination and investigations were done. Results: Among the self-reported toxicity symptoms, cough was the most common acute symptom (59%) while skin problems were the most reported chronic symptoms (11.5%). There was a statistically significant difference regarding age between those with & without blurring of vision [(median, 50 and 39 years respectively) P < .001], muscle spasm [(median, 49 and 40 years respectively) P < .001] and skin problems [(median, 48 & 41 years respectively) P < 0.007]. Regarding duration of exposure, there was a statistical significant difference between those with & without blurring of vision [(median, 10 and 50 years respectively) P < .001], muscle spasm [(median, 10 and 6 years respectively) P < .001] and skin problems [(median, 12 and 6 years respectively) P < .001]. There was statistical significant negative correlation between serum cholinesterase level and age, duration of pesticides exposure and body mass index. Conclusions: The most self-reported pesticides toxicity symptom was cough (59%) while walking problems were the least reported one (5.9%). Age and duration of pesticides exposure are significant risk factors for pesticides toxicity.

Biogenic Synthesis of Zinc Oxide Nanoparticles by Bryophyllum pinnatum and its Acute Oral Toxicity Evaluation in Wistar Rats.

The evaluation of toxic effects of nanoparticles (NPs) has become an important aspect of Nanotechnology research in the 21st century. The present investigation deals with the green synthesis of biogenic zinc oxide nanoparticles (ZnO-NPs) using Bryophyllum pinnatum leaves, their characterization and evaluation of acute oral toxicity in Wistar rats. The characterization of synthesized ZnO-NPs revealed maximum absorbance at 307 nm on UV-Vis spectrophotometric analysis, NTA showed mean size of particles and mode of the particles distribution as 128.2 nm and 12.6 nm, respectively. Zeta potential was found to be -0.369 mV. The absorbance shown by FTIR at 3469, 1644, 1355 and 887 cm-1 indicates the involvement of biomolecules that are accountable for capping and stabilization of ZnO-NPs. The XRD assessment further demonstrated the crystalline nature of the ZnO-NP. The TEM analysis of the synthesized ZnO-NPs revealed the presence of spherical NPs with the mean size of 3.7 nm. The acute oral toxicity evaluation in rat showed an approximate median lethal dose to be more than 2000 mg/kg body weight. It is thus concluded that biogenic ZnO-NPs showed absence of acute oral toxicity symptoms at the doses employed in the present study.

Systemic and Local Biocompatibility Assessment of Graphene Composite Dental Materials in Experimental Mandibular Bone Defect.

The main objective of this research is to demonstrate the biocompatibility of two experimental graphene dental materials by in vitro and in vivo tests for applications in dentistry. The novel graphene dental materials, including one restorative composite and one dental cement, were subjected to cytotoxicity and implantation tests by using a rat model of a non-critical mandibular defect. In vitro cytotoxicity induced by materials on human dental follicle stem cells (restorative composite) and dysplastic oral keratinocytes (dental cement) was investigated at 37 °C for 24 h. After in vivo implantation, at 7 weeks, bone samples were harvested and subjected to histological investigations. The plasma biochemistry, oxidative stress, and sub-chronic organ toxicity analysis were also performed. The resulting cytotoxicity tests confirm that the materials had no toxic effects against dental cells after 24 h. Following graphene dental materials implantation, the animals did not present any symptoms of acute toxicity or local inflammation. No alterations were detected in relative organ weights and in correlation with hepatic and renal histological findings. The materials’ lack of systemic organ toxicity was confirmed. The outcomes of our study provided further evidence on the graphene dental materials’ ability for bone regeneration and biocompatibility.

Evaluation of CB1 antagonists as antidotes for synthetic cannabinoid toxicity in male and female mice

While a plethora of recreational marijuana and cannabis derived products have been legalized across the United States, recent trends also indicate an increase in the number of emergency calls relating to the overdose or accidental exposure to Δ9‐tetrahydrocannabinol (THC) and/or synthetic psychoactive cannabinoids. There are currently no FDA approved medications for treating acute cannabinoid toxicity. To address this public health issue, here we provide key data towards the discovery and development of an effective antidote for treating acute toxicity symptoms that may be associated with cannabis overdose, and by ingestion of certain cannabimimetics such as the potent CB1 receptor agonist JWH‐018. Previously, we established proof‐of‐concept and presented preliminary data showing that the novel CB1 antagonist AM11503 (10 mg/kg, i.v.) effectively reversed the hypothermic effects of an acute dose of JWH‐018 (6 mg/kg, i.p.), effects that were similar to the known CB1 antagonist rimonabant (10 mg/kg, i.v.). Herein, we extend this line of research in male and female CD‐1 mice by: a) examining whether AM11503 induces rimonabant‐like effects on observable behavior; b) assessing the ability of AM11503 to prevent JWH‐018‐mediated tremors and convulsions; and c) comparing the ability of AM11503 and rimonabant to precipitate somatic signs of withdrawal in JWH‐018‐dependent mice. Results show that rimonabant (3.2–32 mg/kg, i.v.) produced a dose‐related increase in scratching and grooming in both male and female mice compared to controls, whereas AM11503 (3.2–32 mg/kg, i.v.) did not alter stereotypic behavior. In interaction studies, administration of 10 mg/kg (i.v.) AM11503 fully blocked tremors and convulsions induced by “suprapharmacological” doses of JWH‐018 (18 mg/kg, i.p.). Finally, rimonabant (10 mg/kg, i.v.) induced significant somatic signs of withdrawal, i.e., head twitches and paw tremors, in male and female mice that were repeatedly exposed to JWH‐018 (3 mg/kg, i.p. once per day for 6 days) compared to vehicle‐treated subjects. In contrast, AM11503 (10 mg/kg, i.v.) did not induce somatic signs of withdrawal in JWH‐018‐dependent mice and effects were similar to vehicle‐treated mice. In conjunction, the inability of AM11503 to produce rimonabant‐like stereotypic behaviors and precipitate somatic signs of withdrawal yet prevent CB1 agonist‐induced acute toxicity allows for the identification and development of safer CB1 antagonist‐based therapies for nullifying synthetic cannabinoid toxicity.Support or Funding InformationFunding Information: Work supported by NIDA/NIH grants R21DA045882 and R41DA044048

Multifunctional compounds lithium chloride and methylene Blue attenuate the negative effects of diisopropylfluorophosphate on axonal transport in rat cortical neurons

Organophosphates (OPs) are valuable as pesticides in agriculture and for controlling deadly vector-borne illnesses; however, they are highly toxic and associated with many deleterious health effects in humans including long-term neurological impairments. Antidotal treatment regimens are available to combat the symptoms of acute OP toxicity, which result from the irreversible inhibition of acetylcholinesterase (AChE). However, there are no established treatments for the long-term neurological consequences of OP exposure. In addition to AChE, OPs can negatively affect multiple protein targets as well as biological processes such as axonal transport. Given the fundamental nature of axonal transport to neuronal health, we rationalized that this process might serve as a general focus area for novel therapeutic strategies against OP toxicity. In the studies described here, we employed a multi-target, phenotypic screening, and drug repurposing strategy for the evaluations of potential novel OP-treatments using a primary neuronal culture model and time-lapse live imaging microscopy. Two multi-target compounds, lithium chloride (LiCl) and methylene blue (MB), which are FDA-approved for other indications, were evaluated for their ability to prevent the negative effects of the OP, diisopropylfluorophosphate (DFP) on axonal transport. The results indicated that both LiCl and MB prevented DFP-induced impairments in anterograde and retrograde axonal transport velocities in a concentration dependent manner. While in vivo studies will be required to confirm our in vitro findings, these experiments support the potential of LiCl and MB as repurposed drugs for the treatment of the long-term neurological deficits associated with OP exposure (currently an unmet medical need).

In-vivo anti-diabetic activity of Capparis erythrocarpos (Capparaceae) root extract

Background Capparis erythrocarpos Isert has been reported to have anti-dyslipidemic effect on normoglycemic animals. However, there are no reports on its effect on the control of blood sugar levels in diabetic animals. Objective This study aimed at investigating the in-vivo antidiabetic activity of C. erythrocarpos in streptozotocin (STZ) induced diabetic mice. Methods Plants materials were collected in April 2018 and the study was conducted from April to July 2019. Antidiabetic activity of hydroethanolic extract of C. erythrocarpos was determined at different doses of 250, 500 and1000 mg/kgbwt and compared to positive and negative controls. Acute antihyperglycemic activity in normal mice was investigated by Oral Glucose Tolerance Test (OGTT) method. Safety of the extract was evaluated by the use of “Up and Down” oral acute toxicity testing method. Statistical differences between groups were assessed by Student’s t-test and one-way ANOVA with Tukey’s multiple comparisons. Results C. erythrocarpos produced significant reduction in fasting blood glucose level compared to the negative control in STZ-induced diabetic mice after 14 days of daily oral doses of the extract at 250 mg/kgbwt (p=0.0267), 500 mg/kgbwt (p=0.0002) and 1000 mg/kgbwt (p=0.0011). OGTT showed that the extract significantly lowered blood glucose levels 2 hours after oral glucose load at all doses provided 100 mg/kgbwt (p=0.0322), 200 mg/kgbwt (p=0.0118) and 500 mg/kgbwt (p=0.0222). There were no statistically significant difference in clinical signs and symptoms of acute oral toxicity observed between control and treatment groups. Conclusion Oral administration of hydroethanolic root extract of C. erythrocarpos is non-acutely toxic and exhibited significant hypoglycemic activity in STZ-induced diabetic mice.

Biochemical and Toxicological Studies of Bridelia micrantha [Berth] and Mitracarpus villosus [Swartz] DC Extracts used as Biofumigant Against Stored Produce Insect Pests on Albino Rats

Background: In recent years, plant materials have been widely explored as sources of insect pest control agents with little or no study on their toxicity. The present study aimed to detect the biochemical alterations in liver and kidney associated with acute oral toxicity of the extracts of B. micrantha and M. villosus in albino rats. Methods: Twenty seven albino rats, weighing between 150-180g were used and divided into nine groups of three rats each, administered with different doses of each extracts (0, 500, 1000, 1500 and 2000mg/kg). The plasma and homogenates of liver and kidney of the rats were investigated for the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALT), total protein, urea and creatinine, using standard laboratory kits. Results: The administration of either extract did not cause death or any hazardous symptoms of acute toxicity, nor resulted in any evident changes in the body weight. However, the extracts caused significant decreases in the levels of ALT, AST, ALP and total protein, urea and creatinine in biochemical parameters. They also caused a significant decrease in the serum parameters of treated rats’ liver and kidney at all doses. Conclusions: The results demonstrated that the oral administration of B. micrantha ethyl acetate extract and of M. villosus petroleum ether extract may be considered as moderately free of toxicity. This was based on our findings that two compounds were moderately safe with respects to their effects on the liver and kidney functions at concentrations of up to 2000 mg/kg body weight of the rats.

Acute oral toxicity test and assessment of combined toxicity of cadmium and aflatoxin B1 in kunming mice

Cadmium and aflatoxin B1 (AFB1) are both common and widespread pollutants in food and feed. There are several reports on toxicity induced by Cadmium or AFB1 alone, but few address the toxicity caused by co-exposure to the two substances. In this study, 42 female and 42 male Kunming (KM) mice were divided into seven groups to test the acute oral toxicity of CdCl2 and AFB1, using Karber's method. The combined toxicity was assessed using the Keplinger evaluation system. Acute toxicity symptoms, deaths, and body and organ weights were evaluated, and hematological, blood biochemical, and histopathological analyses were conducted. The results revealed the following median lethal doses (LD50): LD50(Female KM mice) = 62.56 mg/kg; LD50(Male KM mice) = 48.79 mg/kg; LD50(KM mice)=55.27 mg/kg. The combined toxicity of AFB1 and CdCl2 showed an additive effect in mice, and an increase in the mixed dose of AFB1 and CdCl2 resulted in greater toxicity. These results demonstrated that the combined toxicity of AFB1 and CdCl2 was greater than the toxicities of the individual components in mice; thus, this may cause particular challenges when addressing these hazards in food and feed and the associated risk to human and animal health.

Natural (\u22069-THC) and synthetic (JWH-018) cannabinoids induce seizures by acting through the cannabinoid CB1 receptor

Natural cannabinoids and their synthetic substitutes are the most widely used recreational drugs. Numerous clinical cases describe acute toxic symptoms and neurological consequences following inhalation of the mixture of synthetic cannabinoids known as “Spice.” Here we report that an intraperitoneal administration of the natural cannabinoid Δ9-tetrahydrocannabinol (10 mg/kg), one of the main constituent of marijuana, or the synthetic cannabinoid JWH-018 (2.5 mg/kg) triggered electrographic seizures in mice, recorded by electroencephalography and videography. Administration of JWH-018 (1.5, 2.5 and 5 mg/kg) increased seizure spikes dose-dependently. Pretreatment of mice with AM-251 (5 mg/kg), a cannabinoid receptor 1-selective antagonist, completely prevented cannabinoid-induced seizures. These data imply that abuse of cannabinoids can be dangerous and represents an emerging public health threat. Additionally, our data strongly suggest that AM-251 could be used as a crucial prophylactic therapy for cannabinoid-induced seizures or similar life-threatening conditions.

Hypoglycaemic activity of Mathurameha, a Thai traditional herbal formula aqueous extract, and its effect on biochemical profiles of streptozotocin-nicotinamide-induced diabetic rats

BackgroundThe Thai traditional herbal formula–Mathurameha, consisting of 26 medicinal plants, has been used as an alternative and complementary medicine for diabetes treatment in Wangnamyen Hospital, Thailand. To provide scientific evidences on the efficacy and safety of this herbal formula, in vivo hypoglycaemic activity, effect on serum biochemical profiles and acute toxicity were investigated.MethodsExperimental type 2 diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of nicotinamide 15 min prior to intravenous injection of streptozotocin. The most effective extract from the oral glucose tolerant test (OGTT) was administered daily via the oral route to diabetic rats for 2 weeks. Two-hour postprandial plasma glucose (2h–PPG) levels were measured on days 0, 7, and 14. Biochemical data were measured at the end of daily oral administration experiment.ResultsAqueous extract of the herbal formula was the most potent extract for improving glucose tolerance of streptozotocin-nicotinamide-induced diabetic rats after single oral administration. After 2 weeks of daily oral administration, the aqueous extract showed a dose-dependent glucose lowering effect. At doses of 12.5, 25, and 50 mg/kg, the 2h–PPG level of diabetic rats decreased by 3.32%, 15.78%, and 17.94%, respectively. Most of the biochemical profiles of diabetic rats were improved, including the total cholesterol (TC), alkaline phosphatase (ALP), total protein, albumin, globulin, creatinine, and uric acid levels. The significantly increased triglyceride (TG) level observed in treated diabetic rats indicated a lack of a beneficial effect of the extract on lipid homeostasis. Nevertheless, there were no signs or symptoms of acute toxicity observed after oral administration of aqueous extract (5 g/kg) to both male and female rats.ConclusionsThe results revealed that the herbal formula aqueous extract has hypoglycaemic activity, beneficial effects on biochemical profiles and a lack of acute toxicity. This study confirms the efficacy and safety of the Mathurameha herbal formula used for treating type 2 diabetes mellitus.

Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor

Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice.A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers.

Arylmethylamino steroids as antiparasitic agents

In search of antiparasitic agents, we here identify arylmethylamino steroids as potent compounds and characterize more than 60 derivatives. The lead compound 1o is fast acting and highly active against intraerythrocytic stages of chloroquine-sensitive and resistant Plasmodium falciparum parasites (IC50 1–5 nM) as well as against gametocytes. In P. berghei-infected mice, oral administration of 1o drastically reduces parasitaemia and cures the animals. Furthermore, 1o efficiently blocks parasite transmission from mice to mosquitoes. The steroid compounds show low cytotoxicity in mammalian cells and do not induce acute toxicity symptoms in mice. Moreover, 1o has a remarkable activity against the blood-feeding trematode parasite Schistosoma mansoni. The steroid and the hydroxyarylmethylamino moieties are essential for antimalarial activity supporting a chelate-based quinone methide mechanism involving metal or haem bioactivation. This study identifies chemical scaffolds that are rapidly internalized into blood-feeding parasites.

Stereotactic Radiosurgery for Melanoma Brain Metastases: A Comprehensive Clinical Case Series.

Melanoma has high propensity to metastasize to the brain. With recent gains in improving patient survival, stereotactic radiosurgery (SRS) may offer an effective and less neurotoxic alternative to whole-brain radiation. In the study, we report on the safety and efficacy of SRS in treating melanoma brain metastases in 87 patients. This retrospective multicenter study examined 87 patients with 309 metastases who underwent single-dose or multifractionated SRS for treatment of intracranial metastases from malignant melanoma. A total of 87 patients with a median age of 62 years (26-85) were treated from 2007-2014. Eighty patients (92%) also had extracranial metastases at time of treatment, and 69 patients (79%) had uncontrolled systemic disease. Seventy-nine patients (91%) underwent single-dose fractions, 7 (8%) underwent 3 fractions, and 1 (1%) was treated in 5 fractions. The mean tumor volume (GTV) treated was 1.92 cc. Five patients developed symptoms of acute phase toxicity, and 4 developed late phase toxicity. None had radionecrosis. The median survival was 6months. The Kaplan-Meier 1-year survival rate was 31%, and the 1-year local control rate was 91%. The 1-year survival rate for BRAF-positive patients was 42%, and for BRAF-negative patients it was 27%. Forty-two patients (48%) had distant intracranial recurrences, and 1-year distant control rate was 32%. SRS is a safe and effective treatment option for intracranial metastases from malignant melanoma. This paper serves as a reference for what is achievable in the absence of highly effective systemic therapy.

Phasing out of the Universal Mega Dose of Vitamin-A Prophylaxis to Avoid Toxicity.

Childhood blindness due to corneal ulceration was prevalent among poor Indian children. To tackle this situation, the National Institute of Nutrition (NIN), Hyderabad, India, Vitamin-A (Vit-A) prophylaxis programme was launched nationally in 1970 after field testing. Research of Indian Council for Medical Research (ICMR) documented that prevalence of Vit-A deficiency signs such as Bitot's spot decreased among children, over a period of time. However, this decrease cannot be ascertained is due to mass Vit-A prophylaxis programme. This is because coverage was low and patchy. Improved nutrition status, wider vaccination coverage, increased rate in breast feeding and improvement of healthcare services played a crucial role. Rather many studies revealed that (mass prophylaxis to the child who is having adequate Vit-A level) it may be harmful to certain group of children as a result of acute toxic symptoms. High dose of Vit-A is capable of loss of bone density-hence retarded growth may be observed in susceptible individuals. To tackle this issue food based approach should be promoted (which includes breast feeding) along with timely measles vaccination. The children who have signs of Vit-A deficiency (e.g. night blindness, xeropthalmia, Bitot's spot) or post measles children should receive Vit-A in age specific daily doses for two weeks along with Vit-A rich food, like green leafy vegetables, red palm oil, liver etc. Public spirited citizens, together with scientific community in India, should discourage this “one size fit to all” approach. It will not only avoid the ill effects of high dose of Vit-A but also it will help us optimal utilization of health resources in a resource poor country like India.

Acute Toxicity of Vildagliptin.

This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances. In surviving animals, symptoms were reversible even if treatment was continued. Cynomolgus monkeys from Mauritius appear more sensitive than monkeys of Asian origin. The underlying mechanism(s) of these symptoms in cynomolgus monkeys is currently not well understood, although a vascular mechanism including initial vasoconstriction and subsequent vascular leakage in distal extremities may play a role. The monkey data are reviewed and discussed in the context of other preclinical and clinical data, and it is concluded that acute toxicity following vildagliptin treatment is a monkey-specific phenomenon without relevance for humans.