Delayed Access to Generic Medicine: A Comment on the Hatch-Waxman Act and the Approval Bottleneck

Prescription drug costs can be astronomical. The advent of generic drugs, which sell at substantially lower prices than their brand-name counterparts, can save consumers billions of dollars per year. The Hatch-Waxman Act, which governs the introduction of generic pharmaceuticals into the marketplace, produces an undesired side effect-the approval bottleneck. This Comment examines the approval bottleneck -a potential roadbolock to the generic drug approval process, and comments on attempts to alleviate the problem. This comment suggest that developments in statutes and case law have made leaps in attempting to alleviate the approval bottleneck problem. The Comment evaluate these developments, which include (1) the ability of a subsequent Abbreviated New Drug Application (ANDA) filer to trigger the generic exclusivity period of the first ANDA filer; (2) the forfeiture provisions; (3) declaratory judgments and the relaxed declaratory judgment test; and (4) the rulings on covenants not to sue. Despite these attempts, however, the potential harm to consumers resulting from delayed access to generic medicines remain

Urban Farming Mumbai

Abstract not included

Prime labeling in the context of subdivision of some cycle related graphs

A prime labeling on a graph G of order n is a bijection from the set of vertices of G into the set of first n positive integers such that any two adjacent vertices in G have relatively prime labels. The results about prime labeling of wheel, helm, flower, crown and union of crown graphs are very well-known. In this paper we obtain prime labeling of various graphs resulting from the subdivision of edges in these graphs.Publisher's Versio

Clinical spectrum of dengue in pediatric age group: A study at tertiary care hospital

Background: Dengue is a mosquito-borne human viral disease, which has become a major public health problem recently. The clinical manifestation of dengue infection varies from asymptomatic to severe fatal condition in the form of dengue hemorrhagic fever/dengue shock syndrome. Objectives: The objectives of this study were to study the clinical profile and hematological changes in dengue fever. Materials and Methods: This prospective observational study was carried out at a tertiary care hospital from March 2017 to August 2018. The study population included dengue positive patients admitted to the pediatric ward. All the children age up to 12 years with positive dengue test either NS1 antigen or IgM/IgG antibodies by rapid serological test kit or ELISA were included in the study. Results: Of 105 cases, the most common clinical feature was fever (100%) with raised hematocrit value (45.8%), leukopenia (38.1%), and thrombocytopenia (74%). Conclusion: Hematological profile with thrombocytopenia, raised hematocrit, and leukopenia with raised serum glutamic-pyruvic transaminase gives enough clues to test for dengue serology to reduce the morbidity and mortality by early diagnosis and management of dengue illness

Study of Violent Asphyxial Death

Background:An increasing death rate as a result of violence constitutes a large group in medico-legal autopsies especially deaths due to asphyxia are one of the most important cause in violent deaths.Method: It was a prospective study of all medico-legal autopsies performed between December 2008 and November 2010 at mortuary of Civil Hospital affiliated with B.J.Medical College, Ahmedabad, Gujarat, India. Out of the total autopsies conducted at the Mortuary of Civil Hospital, Ahmedabad, those where the victim died as a result of violent mechanical interference with respiration like hanging, strangulation, and drowning were included.Results and Conclusion:Incidence of violent asphyxia deaths is 5.63% of total autopsies. Hanging (82.48%) is the most commonly encountered violent asphyxia death. Males are most common victims with male:female ratio 1.69:1. Most commonly involved age group is 21-30 years (128 cases forming 32.99% of total) with 200 victims (51.54%) aged 21-40 years. 312 out of 320 cases (97.5%) of hanging were suicidal and rest 8 (2.5%) were accidental in nature. Homicidal hanging is not recorded in present study. All 12 strangulation cases were of homicide, 32 out of 56 (57.14%) cases of drowning were accidental and remaining 24 (42.86%) were suicidal

Architecture of the Short External Rotator Muscles of the Hip.

BackgroundMuscle architecture, or the arrangement of sarcomeres and fibers within muscles, defines functional capacity. There are limited data that provide an understanding of hip short external rotator muscle architecture. The purpose of this study was thus to characterize the architecture of these small hip muscles.MethodsEight muscles from 10 independent human cadaver hips were used in this study (n = 80 muscles). Architectural measurements were made on pectineus, piriformis, gemelli, obturators, quadratus femoris, and gluteus minimus. Muscle mass, fiber length, sarcomere length, and pennation angle were used to calculate the normalized muscle fiber length, which defines excursion, and physiological cross-sectional area (PCSA), which defines force-producing capacity.ResultsGluteus minimus had the largest PCSA (8.29 cm2) followed by obturator externus (4.54 cm2), whereas superior gemellus had the smallest PCSA (0.68 cm2). Fiber lengths clustered into long (pectineus - 10.38 cm and gluteus minimus - 10.30 cm), moderate (obturator internus - 8.77 cm and externus - 8.04 cm), or short (inferior gemellus - 5.64 and superior gemellus - 4.85). There were no significant differences among muscles in pennation angle which were all nearly zero. When the gemelli and obturators were considered as a single functional unit, their collective PCSA (10.00 cm2) exceeded that of gluteus minimus as a substantial force-producing group.ConclusionsThe key findings are that these muscles have relatively small individual PCSAs, short fiber lengths, and low pennation angles. The large collective PCSA and short fiber lengths of the gemelli and obturators suggest that they primarily play a stabilizing role rather than a joint rotating role

Dextransucrase from the mutant of Pediococcus pentosaceus (PPm) is more stable than the wild type

A comparative study on both wild type and mutant of Pediococcus pentosaceus for dextransucrase activity, its stability, dextran synthesizing activity, antibiotic sensitivity and carbohydrate utilization was performed. The wild type P. pentosaceus had specific activity of 0.58 U/mg whereas the mutant showed that of 1.0 U/mg with 72% enhancement. The antibiogram of 27 antibiotics tested against mutant showed significant differences with 9 antibiotics when compared to wild type. In carbohydrate fermentation profile, trehalose, galactose, maltose, lactose and fructose are metabolized by both the strains, but weakly in case of mutant. Stabilization of purified dextransucrase from wild type and mutant with various stabilizers was studied at 30 and 4 °C. Both enzymes were more stable at 4 °C. Among various stabilizers such as dextran (100 kDa, 10 μg/ml), glycerol (0.5%, v/v), PEG 8000 (10 μg/ml) and Tween 80 (0.5%, v/v), Tween 80 provided maximum stabilization at 4 and 30 °C. The mutant showed better stabilization than that of the wild type at both 30 and 4 °C. The loss of activity at 30 °C after 24 h in wild type and mutant in the presence of Tween 80 was only 34 and 32%, respectively, whereas the loss of activity in control of wild type and mutant was 76 and 59%, respectively. After 15 days at 4 °C, the loss of activity in control of wild type and mutant in the presence of Tween 80 was only 15 and 8%, respectively, whereas at 30 °C, the loss of activity in control of wild type and mutant was 49 and 42% respectively. Half-life of the enzyme with Tween 80 was 28.5 and 33.5 h for wild type and mutant, respectively, at 30 °C and 52.1 and 106.6 days for wild type and mutant respectively, at 4 °C

Hypoglycemic activity of Sida spinosa Linn. root extract in Normoglycemic rats.

There is an increased demand of patients to use natural products with antidiabetic activity and ethnobotonical survey conducted revealed that Sida spinosa Linn. root is used in the treatment of diabetes. The present investigation aims to examine the hypoglycemic potential of Sida spinosa Linn. root in normal rats. The root of Sida spinosa Linn. was extracted using ethanol and water and tested for acute toxicity according to OECD 423 guidelines. The ethanolic (SSE) and aqueous (SSA) extracts at 200 and 400 mg/kg b.w. were screened for blood glucose lowering capacity in normal animals (18h fasted rat model) and Glibenclamide (GLB) was used as a standard. Serum glucose (SG) levels were estimated using a glucose oxidase-peroxidase reactive strips and a glucometer. The oral glucose tolerance test (OGTT) was carried out in normal rats. The results of acute toxicity showed that the animals had good tolerance to single doses of SSE/SSA in doses as high as 4000mg/kg and were non-lethal. In OGT test, the normoglycemic rats treated with higher dose SSE, SSA and GLB (10mg/kg) showed 30.36%, 25.24% and 33.21% reduction (P<0.001) in SG level respectively over the period of 120 min compared to normal control group. In single dose one day study, higher dose of SSE, SSA and GLB showed significant (p<0.001) reduction in SG levels (22.3%, 18.2% & 28.6% respectively) at 3h after oral administration. The ethanolic extract (400 mg/kg) was more effective in reducing the SG level in OGTT compared to aqueous extract with improved glucose tolerance. The root of Sida spinosa Linn. has potent hypoglycemic activity in normal rats justifying its use in indigenous system of medicine.Keywords: Diabetes mellitus; Hyperglycemia; OGTT; Serum glucose; Sida spinosa

Glutamate receptor activation triggers OPA1 release and induces apoptotic cell death in ischemic rat retina

PurposeGlutamate receptor activation-induced excitotoxicity has been hypothesized to cause retinal ganglion cell (RGC) death in glaucoma and to link mitochondrial dysfunction in both acute and chronic neurodegenerative disorders. However, the relationships among elevated intraocular pressure (IOP), glutamate receptor-mediated excitotoxicity, and mitochondrial dysfunction in glaucoma remains unknown. The goal of this study was to determine whether the N- methyl D-aspartate (NMDA) glutamate receptor antagonist MK801 can block optic atrophy 1 (OPA1) release and subsequent apoptotic cell death, as well as whether acute IOP elevation triggers OPA1 release and alters OPA1 gene and protein expression in the rat retina after ischemia.MethodsSprague Dawley rats received injections of MK801 (10 mg/kg) or vehicle and then transient retinal ischemia was induced by acute IOP elevation. Following subcellular fractionation, changes in cytoplasmic and mitochondrial OPA1 were assessed by western blot analysis. Also, the expression of OPA1 mRNA was measured by Taqman qPCR, the distribution of OPA1 protein was assessed by immunohistochemistry, and apoptotic cell death was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.ResultsThe ~65 and 90 kDa isoforms of OPA1 were increased in the cytosol in the rat retina at 6 h and at 12 h, but only the 90 kDa isoform of OPA1 was decreased at 12 h after ischemia induced by acute IOP elevation. This suggests that ischemic insult induced OPA1 release from the mitochondria in retinas. Pretreatment with MK801 blocked this effect and significantly increased OPA1 immunoreactivity in the inner retinal layers, as well as OPA1 gene expression and total protein expression in retinas at 12 h after ischemia. Further, pretreatment with MK801 prevented apoptotic cell death in retinas at 12 h after ischemia. Following acute IOP elevation, Bcl-2 mRNA expression in retinas was decreased at 3 h and 6 h but increased at 12 h and 24 h. In contrast, Bax mRNA expression in these retinas was increased in the first 12 h and then plateaued. Moreover, pretreatment with MK801 increased Bcl-2 mRNA expression, but did not alter the course of Bax mRNA expression.ConclusionsThese results indicate that OPA1 release from mitochondria triggered by acute IOP elevation is inhibited by blockade of glutamate receptor activation. Because this effect was accompanied by increases of Bcl-2 expression, no changes of Bax expression, and blockade of apoptosis, these findings indicate that glutamate receptor activation following acute IOP elevation may lead to a distinct mitochondria-mediated cell death pathway in ischemic retina. These results support further studies to determine whether ischemia-induced OPA1 release may be an important component of the biochemical cascade leading to pressure-related ischemic damage in glaucomatous retina