Helicobacter Hypothesis for Idiopathic Parkinsonism: Before and Beyond

We challenge the concept of idiopathic parkinsonism (IP) as inevitably progressive neurodegeneration, proposing a natural history of sequential microbial insults with predisposing host response. Proof-of-principle that infection can contribute to IP was provided by case studies and a placebo-controlled efficacy study of Helicobacter eradication. "Malignant" IP appears converted to "benign", but marked deterioration accompanies failure. Similar benefit on brady/hypokinesia from eradicating "low-density" infection favors autoimmunity. Although a minority of UK probands are urea breath test positive for Helicobacter , the predicted probability of having the parkinsonian label depends on the serum H. pylori antibody profile, with clinically relevant gradients between this "discriminant index" and disease burden and progression. In IP, H. pylori antibodies discriminate for persistently abnormal bowel function, and specific abnormal duodenal enterocyte mitochondrial morphology is described in relation to H. pylori infection. Slow intestinal transit manifests as constipation from the prodrome. Diarrhea may flag secondary small-intestinal bacterial overgrowth. This, coupled with genetically determined intense inflammatory response, might explain evolution from brady/hypokinetic to rigidity-predominant parkinsonism.     

Perception of Human Papillomavirus Infection,Cervical Cancer and HPV Vaccination in North Indian Population

Background

Human Papillomavirus (HPV) -associated cervical cancer is the second-most common cancer in women worldwide but it is the most frequent gynaecological cancer and cancer associated death in India women. The objective of this study was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine acceptance among school and undergraduates students and their parent’s perception about acceptance of HPV vaccine in Northern part of India (Delhi and NCR regions).

Materials and Methods

A qualitative questionnaire based survey among 2500 urban/rural students aged 12–22 years was conducted.

Results

Overall, a low frequency (15%) of HPV and cervical cancer awareness was observed in students and their parents. However, the awareness was much higher in females belonging to urban setup compared to boys with a perception that HPV causes cervical cancer in women only. Additionally, only (13%) participants who were aware of cervical cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of female students were two times more willing to accept HPV vaccination for their ward than male students (p<0.001; OR 95%CI = 2.09 (1.58–2.76).

Conclusion

Cervical cancer and HPV awareness among school, undergraduate students and also to their parents was found to be very low in this part of India. The level of awareness and education appears to be insignificant determinants in rural compared to urban setup. Better health education will be needed to maximize public awareness for cervical cancer prevention.     

Novel 2,2'-[1,2-ethanediylbis(nitriloethylidyne)]-bis-hydroquinone double-wall carbon nanotube paste electrode for simultaneous determination of epinephrine, uric acid and folic acid

The electro-oxidation of epinephrine (EP), uric acid (UA), folic acid (FA), and their mixture has been studied by modified carbon nanotube paste electrode of 2,2'-[1,2-ethanediylbis(nitriloethylidyne)]-bis-hydroquinone using cyclic voltammetry, chronoamperometry and differential pulse voltammetry. This modified electrode exhibited potent and persistent electron mediating behavior followed by well-separated oxidation peaks towards EP, UA and FA with activation overpotential. For the ternary mixture containing EP, UA and FA the three compounds can be well separated from each other at the scan rate of 20mVs(-1). The obtained catalytic peak current, was linearly dependent on the EP, UA and FA concentrations in the range of 0.7-1200muM, 25-750muM and 15-800muM and the detection limits for EP, UA and FA were 0.216+/-0.004, 8.8+/-0.2 and 11.0+/-0.3muM, respectively. The diffusion coefficient (D), and the kinetic parameters such as electron transfer coefficient, (alpha) and heterogeneous rate constant, (k') for EP were also determined using electrochemical approaches. The modified electrode showed good sensitivity, selectivity and stability, and was employed for the determination of EP, UA and FA in the real samples.     

Design,synthesis, and biological evaluation of a cephalosporin-monohydroguaiaretic acid prodrug activated by a monoclonal antibody-beta-lactamase conjugate

A novel cephalosporin derivative of monohydroguaiaretic acid (cephem-M(3)N, 7) was synthesized and found to possess anticancer activity against human leukemia (K562), breast carcinoma (MCF7), human lung cancer (A549), human colon cancer (Colo205) and pancreatic cancer cells (Capan2 and MiaPaCa2). A tumor targeting fusion protein (dsFv3-beta-lactamase) was also used in conjunction with cephem-based M(3)N 7 and its potency toward K562, MCF7, A549, Colo205, Capan2, and MiaPaCa2 was found to approach that of the free M(3)N (4). In the presence of dsFv3-beta-lactamase, tumor cells were found to be much more susceptible to conjugate 7 than normal human embryonic lung (HEL) cells and normal fibroblasts (Hef522). These notions provide a new approach to the use of nordihydroguaiaretic acid (NDGA) and its derivatives for antitumor therapy.     

Trisubstituted and tetrasubstituted pyrazolines as a novel class of cell-growth inhibitors in tumor cells with wild type p53

Derivatives with scaffolds of 1,3,5-tri-substituted pyrazoline and 1,3,4,5-tetra-substituted pyrazoline were synthesized and tested for their inhibitory effects versus the p53^+/+ HCT116 and p53^?/? H1299 human tumor cell lines. Several compounds were active against the two cell lines displaying IC₅₀ values in the low micromolar range with a clearly more pronounced effect on the p53^+/+ HCT116 cells. The compound class shows excellent developability due to the modular synthesis, allowing independent optimization of all three to four key substituents to improve the properties of the molecules.     

Camelus dromedarius Putative Cytochrome P450 Enzyme CYP2E1: Complete Coding Sequence and Phylogenetic Tree

This study determined the full-length sequence of CYP2E1, one of six cytochrome P450 genes previously examined in camel tissues by western blotting and semi-quantitative PCR. The Camelus dromedarius CYP2E1 has an open reading frame of 1,473 bp, and the cDNA encodes a protein of 490 amino acid residues with a molecular weight of 54.8 kDa. The deduced amino acid sequence showed the highest identity with Bos taurus (88%), Sus scrofa (87%), and Homo sapiens (83%). In a phylogenetic analysis, the C. dromedarius CYP2E1 isoform was located beside cattle and pigs. The deduced amino acid sequence of camel CYP2E1 showed the conserved proline-rich amino terminus and the heme-binding signature localized near the carboxy terminus of the protein.     

The Role of Probiotics in the Treatment of Dysentery: a Randomized Double-Blind Clinical Trial

Diarrhea is considered as an important cause of morbidity and mortality, even though one of the main reasons of death following diarrhea is initiated by dysentery. In recent years, the consumption of probiotics has been proposed for the treatment of infectious diarrhea. Despite most of the studies on probiotics have focused on acute watery diarrhea, few studies in the field of dysentery have found beneficial effects of probiotics. This study is a randomized double-blind clinical trial. The patients were randomly placed into control and case groups. In the intervention group, the patients received probiotics in the form of Kidilact® sachet, which contained high amounts of 7-strain friendly bacteria strains of Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium infantis, Bifidobacterium breve, and Streptococcus thermophiles. On the other hand, the patients in the control group received placebo sachets on a daily basis for 5 days. It is notable that the treatment protocol of acute dysentery was done on both groups. The results of this study showed significant differences in the duration of blood in diarrhea between probiotic consumers (2.62 days) and the control group (3.16 days) (P value = 0.05). Additionally, significant differences in the average length of hospitalization in probiotic consumers (3.16 days) and control (3.66 days), (P value = 0.02) could be claimed that the consumption of probiotics is effective in reducing the duration of dysentery and diarrhea. The results of this study suggest that the use of probiotics can be effective in reducing the duration of blood in diarrhea. This study was also recorded in the Iran center of clinical trials registration database (IRCT2014060617985N1).     

Occurrence and Genome Analysis of Cucurbit chlorotic yellows virus in Iran

In 2011 and 2012, several cucurbit‐growing regions of Iran were surveyed and samples with symptoms similar to those induced by Cucurbit chlorotic yellows virus (CCYV) were collected. The pathogen was transmitted to cucumber and melon under greenhouse conditions by whiteflies (Bemisia tabaci). RT‐PCR using designed CCYV‐specific primer pair (CCYV‐F/CCYV‐R) resulted in amplification of the predicted size DNA fragment (870 bp) for the coat protein (CP) gene in samples collected from Boushehr, Eyvanakay and Varamin. Nucleotide sequences of the CP of the three Iranian CCYV isolates were compared with five CCYV isolates obtained from GenBank and analysed. Phylogenetically, all CCYV isolates clustered in two groups; Group I is composed of five non‐Iranian isolates from China, Lebanon, Japan, Sudan and Taiwan, and the three Iranian isolates formed Group 2. Among Iranian isolates, the Eyvanakay isolate clustered in a distinct clade with the Boushehr and Varamin isolates. A phylogenetic tree based on amino acid identity of CP showed that CCYV was closely related to Lettuce chlorosis virus (LCV), Bean yellow disorder virus (BnYDV) and Cucurbit yellow stunting disorder virus (CYSDV). This is the first report of CCYV in Iran.     

Increasing intracellular cAMP and cGMP inhibits cadmium-induced oxidative stress in rat submandibular saliva

The effect of cadmium on induction of oxidative stress in rat submandibular saliva and protective role of increasing intracellular cAMP and cGMP by use of specific phosphodiesterase inhibitors, theophylline and sildenafil were investigated. Pure submandibular saliva was collected intraorally by micro polyethylene cannula from anaesthetized rats using pilocarpine as secretagogue. Acute administration of cadmium (10 mg/kg) caused significant oxidative stress by increasing lipid peroxidation by-products (thiobarbituric reactive substances, TBARS) and decreasing total thiols and total antioxidant power of the saliva. Concurrent therapy of rats by theophylline (25 mg/kg) and sildenafil (5 mg/kg) prevented cadmium-induced oxidative stress in saliva. Theophylline and sildenafil inhibited cadmium-induced increase in lipid peroxidation and decrease in total thiols and antioxidant power. It is concluded that cadmium administration results in oxidative stress in rat submandibular saliva, which can be protected by concurrent administration of specific cyclic nucleotide phosphodiesterase inhibitors.