Objective To examine the association of family organization with metabolic control in adolescents with type 1 diabetes through the mechanisms of family self-efficacy for diabetes and disease management. Method Data from the baseline assessment of a longitudinal RCT were used, wherein 257 adolescent–parent dyads (adolescents aged 11–14) each completed the family organization subscale of the Family Environment Scale, the self-efficacy for Diabetes Self-Management Scale, the Diabetes Behavior Rating Scale, and 2 24-hr diabetes interviews. Results Structural equation modeling showed greater family organization was associated indirectly with better disease management behaviors via greater family self-efficacy (β = .38, p < .001). Greater self-efficacy was indirectly associated with better metabolic control via better disease management both concurrently (β = −.37, p < .001) and prospectively (β = −.26, p < .001). The full model indicates more family organization is indirectly associated with better metabolic control concurrently and prospectively through greater self-efficacy and better disease management (β = −.13, p < .001). Conclusions Understanding the mechanisms by which family organization is associated with metabolic control provides insight into possible avenues of prevention/intervention for better diabetes management.
disease management; family organization; self-efficacy; type 1 diabetes
Indian truck drivers and their younger apprentice drivers are at increased risk of HIV infection. We determine network and risk practices associated with willingness to adopt HIV prevention interventions currently not being used in India: rapid HIV testing, circumcision, and preexposure prophylaxis (PrEP) in order to inform the National AIDS Control Program (NACP). Truck drivers and truck cleaners were systematically recruited to participate in a social network and risk survey in Hyderabad, Southern India. Three separate composite measures of acceptability of rapid HIV testing, circumcision, and PrEP acceptability were utilized to independently assess the relationship of these prevention interventions with risk-practices and social network characteristics. An 89% participation rate yielded 1602 truck drivers and truck cleaners with 54.2% younger than 30 years of age and 2.8% HIV infected. Twenty-five percent of respondents reported sex with female sex workers (FSW) and 5% with men (MSM). Rapid testing, circumcision, and PrEP acceptability were 97.4%, 9.1%, and 85.9%, respectively. Participants reporting prosocial network characteristics were more accepting of rapid testing (adjusted odds ratio [AORs] 3.07–6.71; p<0.05) and demonstrated variable PrEP acceptability (AORs 0.08–2.22; p<0.001). Sex with FSWs was associated with PrEP acceptability (AOR 4.27; p<0.001); sex with MSM was associated with circumcision acceptability only (AOR 2.66; p<0.01). Social network factors and risk-practices were associated with novel prevention acceptability, but not consistently across intervention type and with variable directionality. The NACP will need to consider that intervention uptake may likely be most successful when efforts are targeted to individuals with specific behavior and social network characteristics.
Dengue virus (DENV) is an important human pathogen, especially in the tropical and subtropical parts of the world, causing considerable morbidity and mortality. DENV replication occurs in the cytoplasm; however, a high proportion of nonstructural protein 5 (NS5), containing methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) activities, accumulates in the nuclei of infected cells. The present study investigates the impact of nuclear localization of NS5 on its known functions, including viral RNA replication and subversion of the type I interferon response. By using a mutation analysis approach, we identified the most critical residues within the αβ nuclear localization signal (αβNLS), which are essential for the nuclear accumulation of this protein. Although we observed an overall correlation between reduced nuclear accumulation of NS5 and impaired RNA replication, we identified one mutant with drastically reduced amounts of nuclear NS5 and virtually unaffected RNA replication, arguing that nuclear localization of NS5 does not correlate strictly with DENV replication, at least in cell culture. Because NS5 plays an important role in blocking interferon signaling via STAT-2 (signal transducer and activator of transcription 2) degradation, the abilities of the NLS mutants to block this pathway were investigated. All mutants were able to degrade STAT-2, with accordingly similar type I interferon resistance phenotypes. Since the NLS is contained within the RdRp domain, the MTase and RdRp activities of the mutants were determined by using recombinant full-length NS5. We found that the C-terminal region of the αβNLS is a critical functional element of the RdRp domain required for polymerase activity. These results indicate that efficient DENV RNA replication requires only minimal, if any, nuclear NS5, and they identify the αβNLS as a structural element required for proper RdRp activity.
Monoterpenes, which are among the major components of plant essential oils, are known for their ecological roles as well for pharmaceutical properties. Geraniol, an acyclic monoterpene induces cell cycle arrest and apoptosis/senescence in various cancer cells and plants; however, the genes involved in the process and the underlying molecular mechanisms are not well understood. In this study, we demonstrate that treatment of tomato plants with geraniol results in induction of senescence due to a substantial alteration in transcriptome. We have identified several geraniol-responsive protein encoding genes in tomato using suppression subtractive hybridization (SSH) approach. These genes comprise of various components of signal transduction, cellular metabolism, reactive oxygen species (ROS), ethylene signalling, apoptosis and DNA damage response. Upregulation of NADPH oxidase and antioxidant genes, and increase in ROS level after geraniol treatment point towards the involvement of ROS in geraniol-mediated senescence. The delayed onset of seedling death and induced expression of geraniol-responsive genes in geraniol-treated ethylene receptor mutant (Nr) suggest that geraniol-mediated senescence involves both ethylene dependent and independent pathways. Moreover, expression analysis during tomato ripening revealed that geraniol-responsive genes are also associated with the natural organ senescence process.
Black men who have sex with men (MSM) in the Southeastern United States are disproportionately affected by HIV. Black MSM are more likely to have unrecognized HIV infection, suggesting that testing may occur later and/or infrequently relative to current recommendations. The objective of this qualitative study was to explore the HIV testing behaviors of Black MSM in Atlanta, Georgia, who were participants in the HIV Prevention Trials Network Brothers Study (HPTN 061).
Methods and Findings
We conducted 29 in-depth interviews and four focus groups with a community-recruited sample. Modified grounded theory methodologies were used to guide our inductive analysis, which yielded a typology comprised of four distinct HIV testing patterns. Participants could be categorized as: (1) Maintenance Testers, who tested regularly as part of routine self-care; (2) Risk-Based Testers, whose testing depended on relationship status or sexual behavior; (3) Convenience Testers, who tested irregularly depending on what testing opportunities arose; or (4) Test Avoiders, who tested infrequently and/or failed to follow up on results. We further characterized these groups with respect to age, socioeconomic factors, identity, stigma and healthcare access.
Our findings highlight the heterogeneity of HIV testing patterns among Black MSM, and offer a framework for conceptualizing HIV testing in this group. Public health messaging must account for the diversity of Black MSM's experiences, and multiple testing approaches should be developed and utilized to maximize outreach to different types of testers.
Nicotine is known to generate oxidative stress through cytochrome P450 2A6 (CYP2A6)-mediated metabolism in the liver and other organs, including macrophages. This study has been designed to examine the role of CYP2A6 in nicotine metabolism and oxidative stress in SVGA cells, an immortalized human astrocyte cell line.
SVGA astrocytes were treated with 1μM nicotine, followed by determination of mRNA and protein levels of several CYPs using quantitative RT-PCR and western blot analyses, respectively. Quantitation of nicotine and the nicotine metabolites, cotinine and nicotine-derived nitrosamine ketones (NNK), was performed using an LC-MS/MS method. The generation of reactive oxygen species (ROS) was measured using flow cytometry.
Nicotine significantly upregulated mRNA and protein expression of the most abundantly expressed CYPs in SVGA astrocytes, CYP2A6 and CYP1A1. To characterize the metabolism of nicotine in astrocytes, a highly sensitive LC-MS/MS method was developed which is capable of quantifying very low concentrations of nicotine (0.3ng/ml), cotinine and NNK (0.11ng/ml). The LCMS/MS results showed that nicotine is steadily metabolized to cotinine and NNK from 0.5–4h. Finally, we showed that nicotine initially causes an increase in ROS formation which is then gradually decreased, perhaps due to the increase in superoxide dismutase level. Nicotine metabolism and ROS formation by CYP2A6 were further confirmed by using tryptamine, a selective inhibitor of CYP2A6, which significantly lowered the levels of cotinine and NNK and inhibited ROS formation.
CYP2A6 plays a key role in nicotine metabolism and oxidative stress in astrocytes, and this has implications in nicotine-associated brain toxicity.
Nicotine; CYP2A6; astrocytes; LC-MS/MS; oxidative stress
A study was conducted to identify common arbuscular mycorrhizal (AM) fungi present in rhizosphere of Jatropha curcas L., an important bio-diesel crop, from different arid and semi arid regions of India viz., Jodhpur (Rajasthan), Hissar (Haryana), Jhansi and Lalitpur (Uttar Pradesh) and Hyderabad (Andhra Pradesh). A total of 20 AM species were recorded, which consisted of two species of Acaulospora and 18 species of Glomus. The highest frequency of occurrence was recorded for Glomus intraradix (100%), followed by Acaulospora scrobiculata (83%), G. etunicatum (50%) and Glomus 1 (50%). Maximum species richness was recorded at Jodhpur, followed by Jhansi, Hissar, Hyderabad and Lalitpur. The results seem to suggest that species richness was more in arid regions as compared to semi arid areas.
Acaulospora; Arid and semi arid regions; Arbuscular mycorrhizal fungi; Glomus; Jatropha curcas
Lens epithelium-derived growth factor (LEDGF), a ubiquitously expressed nuclear protein, acts by interacting with DNA and protein and is involved in widely varying cellular functions. Despite its importance, the mechanism(s) that regulate naturally occurring LEDGF activity are unidentified. Here we report that LEDGF is constitutively Sumoylated, and that the dynamical regulatory mechanism(s), Sumoylation and deSumoylation act as a molecular switch in modulating DNA binding and transcriptional activity of LEDGF with the functional consequences. Using bioinformatics analysis coupled with in vitro and in vivo Sumoylation assays, we found that lysine (K) 364 of LEDGF was Sumoylated, repressing its transcriptional activity. Conversely, mutation of K364 to arginine (R) or deSumoylation by Senp-1, a nuclear deSumoylase, enhanced the transactivation capacity of LEDGF and its cellular abundance. The enhancements were directly correlated with an increase in LEDGF’s DNA binding activity and small heat shock protein (Hsps) transcription, while the process was reversed in cells overexpressing Sumo1. Interestingly, cells expressing Sumoylation-deficient pEGFP-K364R protein showed increased cellular survival compared with the wild-type LEDGF protein. The findings provide insights into regulation and regulatory functions of LEDGF in Sumoylation-dependent transcriptional control that may be essential for modifying the physiology of cells to maintain cellular homeostasis. These studies also provide new evidence of the important role of post-translational modification in controlling LEDGF function.
LEDGF; Senp-1; Sumo1; Sp1; Hsp27
We previously suggested links between specific XPD mutations in the fetal genome and the risk of placental maldevelopment and preeclampsia, possibly due to impairment of Transcription Factor (TF)IIH-mediated functions in placenta. To identify the underlying mechanisms, we conducted the current integrative analysis of several relevant transcriptome data sources. Our meta-analysis revealed downregulation of TFIIH subunits in preeclamptic placentas. Our overall integrative analysis suggested that, in the presence of hypoxia and oxidative stress, EGFR signaling deficiency, which can be caused by TFIIH impairment as well as by other mechanisms, results in ATF3 upregulation, inducing mediators of clinical symptoms of preeclampsia such as FLT1 and ENG. EGFR- and ATF3-dependent pathways play prominent roles in cancer development. We propose that dysregulation of these canonical cancer molecular pathways occurs in preeclampsia and delineate the relevance of TFIIH, providing etiologic clues which could eventually translate into a therapeutic approach.
One electron oxidation of neutral sugar radicals has recently been suggested to lead to important intermediates in the DNA damage process culminating in DNA strand breaks. In this work, we investigate sugar radicals in a DNA model system to understand the energetics of sugar radical formation and oxidation. The geometries of neutral sugar radicals C1′•, C2′•, C3′•, C4′• and C5′• of 2′-deoxyguanosine (dG) and 2′-deoxythymidine (dT) were optimized in the gas phase and in solution using the B3LYP and ωB97x functionals and 6-31++G(D) basis set. Their corresponding cations (C1′+, C2′+, C3′+, C4′+ and C5′+) were generated by removing an electron (one-electron oxidation) from the neutral sugar radicals and their geometries were also optimized using the same methods and basis set. The calculation predicts the relative stabilities of the neutral sugar radicals in the order C1′• > C4′• > C5′• > C3′• > C2′•, respectively. Of the neutral sugar radicals, C1′• has the lowest vertical ionization potential (IPvert) ca. 6.33 eV in the gas phase and 4.71 eV in solution. C2′• has the highest IPvert ca. 8.02 eV in the gas phase and the resultant C2′ cation is predicted to undergo a barrierless hydride transfer from the C1′ site to produce the C1′ cation. One electron oxidation of C2′• in dG is predicted to result in a low lying triplet state consisting of G+• and C2′•. The 5′,8-cyclo-2′-deoxyguanosin-7-yl radical formed by intramolecular bonding between C5′• and C8 of guanine transfers spin density from C5′ site to guanine and this structure has IPvert 6.25 eV and 5.48 eV in the gas phase and in solution.
Deoxyribose; sugar radical; ionization potential; oxidation; guanine; deoxyguanosine; 5′,8-cyclo-2′-deoxyguanosine; 2′-deoxythymidine; DFT; sugar cation
The calcium (Ca2+) transporters, like Ca2+ channels, Ca2+ ATPases, and Ca2+ exchangers, are instrumental for signaling and transport. However, the mechanism by which they orchestrate the accumulation of Ca2+ in grain filling has not yet been investigated. Hence the present study was designed to identify the potential calcium transporter genes that may be responsible for the spatial accumulation of calcium during grain filling. In silico expression analyses were performed to identify Ca2+ transporters that predominantly express during the different developmental stages of Oryza sativa. A total of 13 unique calcium transporters (7 from massively parallel signature sequencing [MPSS] data analysis, and 9 from microarray analysis) were identified. Analysis of variance (ANOVA) revealed differential expression of the transporters across tissues, and principal component analysis (PCA) exhibited their seed-specific distinctive expression profile. Interestingly, Ca2+ exchanger genes are highly expressed in the initial stages, whereas some Ca2+ ATPase genes are highly expressed throughout seed development. Furthermore, analysis of the cis-elements located in the promoter region of the subset of 13 genes suggested that Dof proteins play essential roles in regulating the expression of Ca2+ transporter genes during rice seed development. Based on these results, we developed a hypothetical model explaining the transport and tissue specific distribution of calcium in developing cereal seeds. The model may be extrapolated to understand the mechanism behind the exceptionally high level of calcium accumulation seen in grains like finger millet.
To promote the remineralization by ionic exchange mechanism instead of invasive techniques many remineralizing agents can be used.
To evaluate the remineralization effects of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on white spot lesions (WSLs) and its inhibitory effect on Streptococcus mutans colonization.
Materials and Methods:
The study group consisted of 60 subjects exhibiting at least 1-WSL. Subjects were randomly divided into 2 groups: A test group using CPP-ACP cream (GC-Tooth Mousse, Leuven, Belgium) and a control group using only fluoride containing toothpaste for a period of 3-month. Baseline WSLs were scored using DIAGNOdent device (KaVo Germany) and the saliva samples were collected to measure S. mutans counts. After the 3-month period the WSLs were again recorded and the saliva collection was repeated.
DIAGNOdent measurements were increased by time (P = 0.002) in the control group and no statistically significant difference (P = 0.217) was found in the test group by the 3-month period. In both groups, the mutans counts were decreased in the 3-month experimental period.
These clinical and laboratory results suggested that CPP-ACP containing cream had a slight remineralization effect on the WSL in the 3-month evaluation period however, longer observation is recommended to confirm whether the greater change in WSLs is maintained.
Casein phosphopeptide-amorphous calcium phosphate; enamel; remineralization; white-spotlesions
The traditional approach to atlantoaxial subluxation which is irreducible after traction is transoral decompression and reduction or odontoid excision and posterior fixation. Transoral approach is associated with comorbidities. However using a posterior approach a combination of atlantoaxial joint space release and a variety of manipulation procedures, optimal or near optimal reduction can be achieved. We analysed our results in this study based on above procedure.
Materials and Methods:
66 cases treated over a 5 year period were evaluated retrospectively. Three cases treated by occipito cervical fusion were not included in the study. The remaining 63 cases were classified into three types. All except two cases were subjected to primary posterior C1-C2 joint space dissection and release followed by on table manipulation which was tailored to treat the type of atlantoaxial subluxation. Optimal or near optimal reduction was possible in all cases. An anterior transoral decompression was needed only in two cases where a bony growth (callus) between the C1 anterior arch and the odontoid precluded reduction by posterior manipulation. All cases then underwent posterior fusion and fixation procedures. Patients were neurologically and radiologically evaluated at regular followups to assess fusion and stability for a minimum period of 6 months.
Of the 63 cases who underwent posterior manipulation, 49 cases achieved optimum reduction and the remaining 14 cases showed near optimal reduction. Two cases expired in the postoperative period. None of the remaining cases showed neurological worsening after the procedure. Evaluation at 6 months after surgery revealed good stability and fusion in all except three cases.
Atlantoaxial joint release and manipulation can be used to achieve reduction in most cases of atlantoaxial subluxation, obivating the need of transoral odontoid excision.
Atlantoaxial joint release; atlantoaxial subluxation; cervical spine injuries
Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-Rs), dopamine transporter (DAT) binding potential (BP), and amphetamine (AMP)-induced dopamine release (DArel) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects.
As compared with controls, DArel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D2-R increase in left ventral striatum. SERT binding potential in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS−OCD). In 3 subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DArel and 5-HT2A BP, when compared with TS−OCD subjects and normal controls.
The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DArel is a primary defect in TS (Singer et al, 2002). The finding of decreased SERT BP, and the possible elevation in 5-HT2aR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.
Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15–20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored.
The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain.
The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates.
Extra-pulmonary Tuberculosis; Next-generation Sequencing; Genetic Heterogeneity; Single Nucleotide Variations; Insertion Elements; Phylogeny; Spoligotyping
Mutations in XPD (ERCC2), XPB (ERCC3), and TTD-A (GTF2H5), genes involved in nucleotide excision repair and transcription, can cause several disorders including trichothiodystrophy (TTD) and xeroderma pigmentosum (XP). In this study, we tested the hypothesis that mutations in the XPD gene affect placental development in a phenotype-specific manner. To test our hypothesis and decipher potential biologic mechanisms, we compared all XPD-associated TTD (n=43) and XP (n=37) cases reported in the literature with respect to frequencies of gestational complications. Our genetic epidemiologic investigations of TTD and XP revealed that the exact genetic abnormality was relevant to the mechanism leading to gestational complications such as preeclampsia. Through structural mapping, we localized the preeclampsia-associated mutations to a C-terminal motif and the helicase surfaces of XPD, most likely affecting XPD's binding to cdk-activating kinase (CAK) and p44 subunits of transcription factor (TF) IIH. Our results suggested a link between TTD- but not XP-associated XPD mutations, placental maldevelopment and risk of pregnancy complications, possibly due to impairment of TFIIH-mediated functions in placenta. Our findings highlight the importance of the fetal genotype in development of gestational complications, such as preeclampsia. Therefore, future studies of genetic associations of preeclampsia and other placental vascular complications may benefit from focusing on genetic variants within the fetal DNA.
trichothiodystrophy; xeroderma pigmentosum; XPD; TFIIH; human fetal development
A study was conducted to identify suitable arbuscular mycorrhizal (AM) fungi for inoculation of Bambusa bambos and Dendrocalamus strictus at nursery stage for increasing growth and productivity. Twelve AM species, isolated from bamboo and other common trees of Bundelkhand were used for inoculations. In B. bambos, total dry weight and phosphorus (P) uptake were significantly increased by all studied fungi and shoot length was increased by eight AM inoculants. Maximum mycorrhizal dependency (MD) was recorded for Acaulospora scrobiculata (44.2%), followed by Glomus cerebriforme (41.6%) and G. intraradix (41.0%). In D. strictus, all tested AM inoculants significantly increased shoot length, dry shoot weight and P uptake, except Glomus 1. Dry root weight was significantly increased by only two inoculants namely, G. cerebriforme and G. etunicatum. Total dry weight was significantly increased by eight AM fungi. Maximum MD was recorded for G. cerebriforme (62.9%), followed by G. diaphanum (55.0%) and G. etunicatum (51.3%). Thus, the results showed that utilization of effective AM fungi can enhance the productivity of bamboo in the region.
Arbuscular mycorrhizal fungi; Bambusa bambos; Biomass productivity; Dendrocalamus strictus; Seedling growth
Laryngocele is a benign condition due to abnormal dilatation of the laryngeal saccule. Localized amyloidosis causing laryngocele is a rare entity with few reports in the literature. We present a young male patient with a large combined laryngocele secondary to laryngeal amyloidosis.
Laryngocele; Amyloidosis; Combined laryngocele; Laryngeal amyloidosis; Neck swelling; Laryngeal saccule
Extremophiles are the microorganisms which can survive under extreme conditions of temperature, pressure, pH, salinity etc. They have gained much attention for their potential role in biotechnological and industrial applications. The large amount of experimental data in the literature is so diverse, that it becomes difficult and time consuming for the researcher to implement it in various areas of research. Therefore, a systematic arrangement of data and redirection in a similar fashion through web interface can assist researchers in analyzing the data as per their requirement. ExtremeDB is a freely available web based relational database which integrates general characteristics, genome-proteome information, industrial applications and recent scientific investigations of the seven major groups of 865 extremophillic microorganisms. The search options are user friendly and analyses tools such as Compare and Extreme BLAST have been incorporated for comparative analysis of two or more extremophiles and determining the sequence similarity of a given protein/nucleotide in relation to other extremophiles respectively. The effort put forth herein in the form of database, would open up new avenues on the potential utility of extremophiles in applied research. ExtremeDB is freely accessible via http://extrem.igib.res.in.
Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats.
Rats undergone olfactory bulbs ablations were analyzed after post-surgical rehabilitation period of 2 weeks. Animals were then treated with different doses of curcumin (100, 200 and 400 mg/kg; p.o.), piperine (20 mg/kg; p.o.) and their combination daily for another 2 weeks. Imipramine (10 mg/kg; i.p.) served as a standard control. Various behavioral tests like forced swim test (FST), open field behaviour and sucrose preference test (SPT) were performed, followed by estimation of biochemical, mitochondrial, molecular and histopathological parameters in rat brain.
Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in FST, hyperactivity in open field arena, and anhedonic like response in SPT along with alterations in mitochondrial enzyme complexes, increased serum corticosterone levels and oxidative damage. These deficits were integrated with increased inflammatory cytokines (TNF-α) and apoptotic factor (caspase-3) levels along with a marked reduction in neurogenesis factor (BDNF) in the brain of olfactory bulbectomized (OBX) rats. Curcumin treatment significantly and dose-dependently restored all these behavioral, biochemical, mitochondrial, molecular and histopathological alterations associated with OBX induced depression. Further, co-administration of piperine with curcumin significantly potentiated their neuroprotective effects as compared to their effects alone.
The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.
Intraocular gnathostomiasis is a rare parasitic infection caused by the third-stage larvae of spiruroid nematode Gnanthostoma spp. seen mostly in tropical and subtropical regions. It is a food-borne zoonosis caused by ingestion of raw or undercooked freshwater fish, amphibians, reptiles, birds, and mammals, all of which are known to harbor advanced third-stage larvae of Gnanthostoma spp. To date, 74 cases of intraocular gnathostomiasis have been reported from 12 different countries. Only four countries have reported more than 10 cases each, and India shares the rare distinction of being one of them, with 14 cases. Surprisingly, not a single case of cutaneous gnanthostomiasis has ever been reported from India. We present one such case of intraocular gnathostomiasis in a 41-year-old male who presented with an actively motile worm attached to the iris, and we review the pertinent literature of all such cases reported from India.
Utilizing postmortem data (Breese, et al., 2000), we hypothesized that the densities of high-affinity neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) in the brain exist in a continuum from highest to lowest as follows: smokers without schizophrenia > smokers with schizophrenia > nonsmokers without schizophrenia > nonsmokers with schizophrenia. Application of the Kruskal-Wallis Test (Stata, 2003) to the postmortem data (Breese, et al., 2000) confirmed the hypothesized order in the cortex and the hippocampus and attained significance in the caudate and the thalamus.
Positron emission tomography (PET) was performed for 60 minutes at 6 hours after the intravenous administration of 444 megabequerels [MBq] (12 mCi) 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA), a radiotracer for high-affinity neuronal α4β2 nAChRs, as a bolus plus continuous infusion to 10 adults (7 men and 3 women) (6 smokers including 5 with paranoid schizophrenia and 4 nonsmokers) ranging in age from 22 to 56 years (mean 40.1, standard deviation 13.6). The thalamic nondisplaceable binding potential (BPND) was 1.32 ± 0.19 (mean ± standard deviation) for healthy control nonsmokers; 0.50 ± 0.19 for smokers with paranoid schizophrenia; and 0.51 for the single smoker without paranoid schizophrenia. The thalamic BPNDs of nonsmokers were significantly higher than those of smokers who smoked cigarettes a few hours before the scans (P = 0.0105) (StataCorp, 2003), which was likely due to occupancy of nAChRs by inhaled nicotine in smokers. Further research is needed to rule out the effects of confounding variables.
nicotinic acetylcholine receptor; Kruskal-Wallis H Statistic; rank sum tests
Corynebacterium pseudotuberculosis is a pathogen of great veterinary and economic importance, since it affects livestock, mainly sheep and goats, worldwide, together with reports of its presence in camels in several Arabic, Asiatic, and East and West African countries, as well as Australia. In this article, we report the genome sequence of Corynebacterium pseudotuberculosis strain Cp162, collected from the external neck abscess of a camel in the United Kingdom.
Factitious biochemical reports result in the misguiding of clinicians, unnecessary retesting, wrong diagnoses and incorrect treatments. A vigilant biochemist identifies these factitious biochemical reports and alerts the clinician regarding the proper interpretation of the biochemical reports, thus preventing a misdiagnosis and an incorrect treatment. We are presenting a case report of a multiple myeloma patient who presented with factitious biochemical reports which were caused due to paraproteinaemia. In the present case, the patient presented with an underestimation of urea and creatinine, an underestimation of sodium, low albumin levels and high phosphate levels. On repeating the same tests after dilutions and deproteinizing, the effects of the paraproteins on the above mentioned tests were reduced. Thus, from the observations of our study, we suggest that the interference by paraproteinaemia can be reduced by analyzing the biochemical parameters after dilution and deproteinization.
Paraproteinemia; Multiple myeloma; Deproteinization