Drug-prescribing patterns during pregnancy in the tertiary care hospitals of Pakistan: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The rationale for use of drugs during pregnancy requires a careful assessment as in addition to the mother, the health and life of her unborn child is also at stake. Information on the use of drugs during pregnancy is not available in Pakistan. The aim of this study was to evaluate the patterns of drug prescriptions to pregnant women in tertiary care hospitals of Pakistan.</p> <p>Methods</p> <p>This was a cross-sectional study conducted at five tertiary care hospitals of Pakistan. Copies of outpatient medicinal prescriptions given to pregnant patients attending the antenatal clinics were collected. The drugs were classified according to the pharmacological class and their teratogenic potential.</p> <p>Results</p> <p>All the pregnant women attending the antenatal clinics received a prescription containing at least one drug. A total of 3769 distinct prescriptions given to different women were collected. Majority of the women who received the prescriptions belonged to third trimester (55.4%) followed by second (33.6%) and first trimester (11.0%). On an average, each prescription contained 1.66 ± 0.14 drugs. The obstetricians at Civil Hospital, Karachi and Chandka Medical College Hospital, Larkana showed a tendency of prescribing lesser number of drugs compared to those in other hospitals. Anti-anemic drugs including iron preparations and vitamin and mineral supplements (79.4%) were the most frequently prescribed drugs followed by analgesics (6.2%) and anti-bacterials (2.2%). 739 women (19.6%) received prescriptions containing drugs other than vitamin or mineral supplements. Only 1275 (21.6%) of all the prescribed drugs (n = 6100) were outside this vitamin/mineral supplement class. Out of these 1275 drugs, 29 (2.3%) drugs were prescribed which are considered to be teratogenic. Misoprostol was the most frequently prescribed (n = 6) among the teratogenic drugs followed by carbimazole (n = 5) and methotrexate (n = 5). Twenty nine pregnant women (0.8% of all the women studied) were prescribed these teratogenic drugs.</p> <p>Conclusion</p> <p>Less than one percent of the pregnant women attending tertiary care hospitals in Pakistan are prescribed teratogenic drugs. The prescribing practices of Pakistani physicians are similar to those in western countries.</p

In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a potential strategy for treatment of macular degenerations

The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration

Photoactivatable drugs for nicotinic optopharmacology

Photoactivatable pharmacological agents have revolutionized neuroscience, but the palette of available compounds is limited. We describe a general method for caging tertiary amines by using a stable quaternary ammonium linkage that elicits a red shift in the activation wavelength. We prepared a photoactivatable nicotine (PA-Nic), uncageable via one- or two-photon excitation, that is useful to study nicotinic acetylcholine receptors (nAChRs) in different experimental preparations and spatiotemporal scales

Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6nclfmice presented mainly with photoreceptor degeneration, supplementation of CLN6 in photoreceptors was not beneficial. Because the level of CLN6 is low in photoreceptors but high in bipolar cells (retinal interneurons that are only lost in Cln6-deficient mice at late disease stages), we explored the therapeutic effects of delivering CLN6 to bipolar cells using adeno-associated virus (AAV) serotype 7m8. Bipolar cell-specific expression of CLN6 slowed significantly the loss of photoreceptor function and photoreceptor cells. This study shows that the deficiency of a gene normally expressed in bipolar cells can cause the loss of photoreceptors and that this can be prevented by bipolar cell-directed treatment

Structuring of Bacterioplankton Diversity in a Large Tropical Bay

Structuring of bacterioplanktonic populations and factors that determine the structuring of specific niche partitions have been demonstrated only for a limited number of colder water environments. In order to better understand the physical chemical and biological parameters that may influence bacterioplankton diversity and abundance, we examined their productivity, abundance and diversity in the second largest Brazilian tropical bay (Guanabara Bay, GB), as well as seawater physical chemical and biological parameters of GB. The inner bay location with higher nutrient input favored higher microbial (including vibrio) growth. Metagenomic analysis revealed a predominance of Gammaproteobacteria in this location, while GB locations with lower nutrient concentration favored Alphaproteobacteria and Flavobacteria. According to the subsystems (SEED) functional analysis, GB has a distinctive metabolic signature, comprising a higher number of sequences in the metabolism of phosphorus and aromatic compounds and a lower number of sequences in the photosynthesis subsystem. The apparent phosphorus limitation appears to influence the GB metagenomic signature of the three locations. Phosphorus is also one of the main factors determining changes in the abundance of planktonic vibrios, suggesting that nutrient limitation can be observed at community (metagenomic) and population levels (total prokaryote and vibrio counts)

Abrolhos Bank Reef Health Evaluated by Means of Water Quality, Microbial Diversity, Benthic Cover, and Fish Biomass Data

The health of the coral reefs of the Abrolhos Bank (southwestern Atlantic) was characterized with a holistic approach using measurements of four ecosystem components: (i) inorganic and organic nutrient concentrations, [1] fish biomass, [1] macroalgal and coral cover and (iv) microbial community composition and abundance. The possible benefits of protection from fishing were particularly evaluated by comparing sites with varying levels of protection. Two reefs within the well-enforced no-take area of the National Marine Park of Abrolhos (Parcel dos Abrolhos and California) were compared with two unprotected coastal reefs (Sebastião Gomes and Pedra de Leste) and one legally protected but poorly enforced coastal reef (the “paper park” of Timbebas Reef). The fish biomass was lower and the fleshy macroalgal cover was higher in the unprotected reefs compared with the protected areas. The unprotected and protected reefs had similar seawater chemistry. Lower vibrio CFU counts were observed in the fully protected area of California Reef. Metagenome analysis showed that the unprotected reefs had a higher abundance of archaeal and viral sequences and more bacterial pathogens, while the protected reefs had a higher abundance of genes related to photosynthesis. Similar to other reef systems in the world, there was evidence that reductions in the biomass of herbivorous fishes and the consequent increase in macroalgal cover in the Abrolhos Bank may be affecting microbial diversity and abundance. Through the integration of different types of ecological data, the present study showed that protection from fishing may lead to greater reef health. The data presented herein suggest that protected coral reefs have higher microbial diversity, with the most degraded reef (Sebastião Gomes) showing a marked reduction in microbial species richness. It is concluded that ecological conditions in unprotected reefs may promote the growth and rapid evolution of opportunistic microbial pathogens

Age-dependent effects of low-dose nicotine treatment on cocaine-induced behavioral plasticity in rats

Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a “gateway” drug that sensitizes reward pathways to the addictive effects of other psychostimulants. To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06&nbsp;mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0&nbsp;mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3&nbsp;days with saline or cocaine (0.4&nbsp;mg/kg, i.v.), and, after 1&nbsp;day of withdrawal, were given a challenge dose of cocaine (0.4&nbsp;mg/kg, i.v.). Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2–4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats

Regulatory Response to Carbon Starvation in Caulobacter crescentus

Bacteria adapt to shifts from rapid to slow growth, and have developed strategies for long-term survival during prolonged starvation and stress conditions. We report the regulatory response of C. crescentus to carbon starvation, based on combined high-throughput proteome and transcriptome analyses. Our results identify cell cycle changes in gene expression in response to carbon starvation that involve the prominent role of the FixK FNR/CAP family transcription factor and the CtrA cell cycle regulator. Notably, the SigT ECF sigma factor mediates the carbon starvation-induced degradation of CtrA, while activating a core set of general starvation-stress genes that respond to carbon starvation, osmotic stress, and exposure to heavy metals. Comparison of the response of swarmer cells and stalked cells to carbon starvation revealed four groups of genes that exhibit different expression profiles. Also, cell pole morphogenesis and initiation of chromosome replication normally occurring at the swarmer-to-stalked cell transition are uncoupled in carbon-starved cells

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy