4-Methyl-2,6-diformylphenol based biocompatible chemosensors for pH: discrimination between normal cells and cancer cells

Two compounds, namely, 2-hydroxy-5-methyl-3-((pyridin-2-ylimino)methyl)benzaldehyde (HM-2py-B) and 2-hydroxy-5-methyl-3-((pyridin-3-ylimino)methyl)benzaldehyde (HM-3py-B), have been explored as fluorescent chemosensors for pH. HM-2py-B and HM-3py-B were synthesized by single step condensation reaction between 4-methyl-2,6-diformylphenol and the appropriate aminopyridine. These compounds have been characterized by elemental analysis, FT-IR, ¹H NMR, ¹³C NMR, ESI mass spectrometry, and absorption and fluorescence spectroscopy. Their structures have been confirmed by single crystal X-ray diffraction analysis. Both of the compounds show low emission at 530 nm at low pH. Fluorescence intensity increases with the increase in pH. With the alteration in pH of the medium from 4.0 to 10.0, the fluorescence intensity at 530 nm enhances by 66 and 195 fold for HM-2py-B and HM-3py-B, respectively. pK_a values of HM-2py-B and HM-3py-B have been determined to be 7.15 and 6.57, respectively. Fluorescence increase occurs mainly due to deprotonation of the phenolic OH group. Several cations and anions could not induce significant change in fluorescence behavior for both of the probes. The quantum yield and life-time enhance significantly when the pH of the medium is changed from 5.0 to 9.0. Naked eye identification of different pH environments is possible by using these compounds. Some theoretical calculations have been carried out to support experimentally obtained spectral transitions. As cancer cell has a pH in the range of 5.5–7.0 in comparison to normal cell pH of 7.4, these probes have been used effectively to discriminate between normal cells and cancer cells.

Two 4-methyl-2,6-diformylphenol based compounds with pyridylamine have been established as chemosensors for pH. The probes are able to differentiate between normal cells and cancer cells.     

Randomized controlled trial of effectiveness of lafutidine versus pantoprazole in uninvestigated dyspepsia

Objectives:

Lafutidine is a new H₂-blocker in India claimed to be more potent and effective than existing H₂-blockers. Proton pump inhibitors (PPIs), by virtue of their mechanism of action, have greater efficacy than H₂-blockers in gastric acid suppression. However, clinical trials comparing H₂-blockers directly with PPIs are limited. We carried out a head-to-head comparison of the effectiveness of lafutidine versus the PPI pantoprazole in uninvestigated dyspepsia [CTRI/2013/12/004261].

Materials and Methods:

A prospective, open label, randomized, controlled trial was conducted in a tertiary care hospital. Ambulatory adult patients with dyspepsia, not yet subjected to endoscopy, were recruited if they had at least moderately severe symptoms, defined as a score of ≥ 4 on a 7-point Global Overall Symptom (GOS) Scale. Those with alarm features or significant comorbidity were excluded. Subjects received either once daily lafutidine 10 mg or pantoprazole 40 mg, orally, for 8 weeks. Reflux, dysmotility and pain scores were assessed by Modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSGERD), and quality of life (QoL) by SF-8 scale. The latter had physical and mental components summarized by physical component summary score (PCS) and a mental component summary score (MCS).

Results:

Of 122 patients enrolled, data of 57 on lafutidine and 60 on pantoprazole were analyzed. At 4 weeks, proportion of subjects responding (GOS score ≤ 2) in the two arms (lafutidine 45.61% vs. pantoprazole 48.33%, P = 0.854) or showing symptom resolution (GOS score ≤ 1) (lafutidine 12.28% vs. pantoprazole 5.00%; P = 0.197) were comparable. Similarly at 8 weeks, both responder (lafutidine 52.63% vs. pantoprazole 56.67%; P = 0.712) and symptom resolution proportions (lafutidine 33.33% vs. pantoprazole 30%; P = 0.843) were comparable. Total score on mFSSGERD scale, as well as all its three component scores, and PCS and MCS scores on QoL SF-8 scale showed improvement but no statistically significant difference between the two arms. Tolerability of both drugs was excellent.

Conclusions:

Lafutidine is well-tolerated and there is no clinically worthwhile difference between the two drugs in the empirical treatment of uninvestigated dyspepsia.KEY WORDS: Dyspepsia, lafutidine, pantoprazole, randomized controlled trial     

The burden of diabetes and impaired fasting glucose in India using the ADA 1997 criteria: prevalence of diabetes in India study (PODIS)

This random multistage cross sectional population survey was undertaken to determine the prevalence of diabetes mellitus (DM) and impaired fasting glycemia/glucose (IFG) in subjects aged 25 years and above in India. The study was carried out in 108 centers (49 urban and 59 rural) to reflect the size and heterogeneity of the Indian population. 41,270 (20,534 males and 20,736 females) subjects were studied. 21,516 (10,865 males and 10,651 females) were from urban areas and 19,754 (9669 males and 10,085 females) from rural areas. Blood samples were taken after a fast of 10-12h and the subjects were categorized as having IFG or DM using the 1997 American Diabetes Association criteria. The age and gender standardized prevalence rate for DM and IFG in the total Indian population was 3.3 and 3.6% respectively (P < 0.001). The standardized prevalence of DM and IFG in urban areas was significantly higher than that for the rural population (urban DM prevalence 4.6% versus rural DM prevalence 1.9%, P < 0.001; urban IFG prevalence 4.8% versus rural IFG prevalence 2.5%, P < 0.001). There was no statistically significant difference in the prevalence between DM (4.6%) and IFG (4.8%) in the urban population. The rural prevalence of IFG (2.5%) was significantly (P <0.001) more than the rural prevalence of DM (1.9%). Type 2 diabetes is a major health problem is India.     

Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.     

6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.     

Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression

Objective

The present study aimed to investigate whether graded doses of Bacopa Monniera (BM) extract could produce antidepressant-like effects in chronic unpredictable stress (CUS) induced depression in rats and its possible mechanism(s).

Methods

Rats were subjected to an experimental setting of CUS. The effect of BM extract treatment in CUS-induced depression was examined using behavioral tests including the sucrose consumption, open field test and shuttle box escape test. The mechanism underlying the antidepressant-like action of BM extract was examined by measuring brain-derived neurotrophic factor (BDNF) protein and mRNA expression in brain tissues of CUS-exposed rats.

Results

Exposure to CUS for 4 weeks caused depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity and escape latency. In addition, it was found that BDNF protein and mRNA levels in the hippocampus and frontal cortex were lower in CUS-treated rats, as compared to controls. Daily administration of the graded doses of BM extract during the 4-week period of CUS significantly suppressed behavioral changes and attenuated the CUS-induced decrease in BDNF protein and mRNA levels in the hippocampus and frontal cortex.

Conclusion

The results suggest that BM extract alleviates depression induced by CUS. Present study also confirms that 80-120 mg/kg doses of BM extract have significantly higher antidepressant-like activity.     

胃、结直肠癌术前区域性动脉化疗几个相关问题

胃、结直肠癌根治性切除术复发转移是严重影响术后5 a生存率提高的重要原因.以手术为主综合治疗已成为新的趋势,其中术前区域性动脉化疗(preoperative regional-arterial chemotherapy,PRAC)尤为值得重视.本文介绍了术前PRAC的概念、作用机制和影响区域性动脉化疗疗效的相关因素,并就术前区域性动脉化疗在胃、结直肠癌综合治疗中的评价进行讨论.