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1.
Environ Health Insights ; 18: 11786302241257819, 2024.
Article in English | MEDLINE | ID: mdl-38863689

ABSTRACT

Background: The usage of solid cooking fuels is widely prevalent in low and middle-income countries, including India, and contributes to indoor air pollution (IAP), which has detrimental health effects. Moreover, time spent inside the house increases as people age. In this context, the present study tried to understand the association between exposure to indoor air pollution and unhealthy symptoms, including shortness of breath, dizziness, headache, fatigue, wheezing, and cough among middle-aged and older adults in India. Methods: We extracted the unit-level individual data (N = 63 790) from the Longitudinal Aging Study in India (LASI)-Wave 1 (2017-2018). The statistical analyses used were Chi-square test and binary logistic regression, which estimated the odds ratio to identify the determinants of the unhealthy symptoms. Results: The odds of shortness of breath (adjusted OR: 1.14, 99% CI: 1.05-1.23), dizziness (adjusted OR: 1.28, 99% CI: 1.21-1.35), fatigue (adjusted OR: 1.32, 99% CI: 1.26-1.39), wheezing (adjusted OR: 1.30, 99% CI: 1.19-1.42), and cough (adjusted OR: 1.36, 99% CI: 1.27-1.45) were higher among individuals from households where solid cooking fuels was used. Similarly, the odds of shortness of breath, headache, wheezing, and cough were higher among individuals with a household member who smoked inside the house. The results indicated that the odds of shortness of breath, headache, and cough were significantly lower among participants exposed to incense use. Conclusion: Based on the results of this study, we suggest developing programs to combat the sources of indoor air pollution and the associated unhealthy symptoms, especially in rural settings. It is also important to bring awareness and practice clean fuel usage at individual and community levels to improve population health.


This study is the first of its kind to explore indoor air pollution and unhealthy symptoms among a large sample in India. We believe it will contribute significantly to the global literature on indoor pollution and health outcomes.

2.
J Forensic Odontostomatol ; 41(2): 2-9, 2023 Aug 27.
Article in English | MEDLINE | ID: mdl-37634171

ABSTRACT

Sex determination or sex estimation from a single or fragment of bone is always difficult in the absence of other bones from the same individual. The current study was an attempt to estimate the sex of an individual from the posterior ramus of mandible or the mandibular ramus flexure. A retrospective study was conducted using orthopantomographs (OPGs) of 200 males and 200 females between the age group of 20 - 70 years. Each radiographic image was examined for the presence of a flexure or notching on the posterior border of the ramus in relation to occlusal plane as the method followed by Loth & Henneberg 1996.The study resulted in samples that were correctly classified as females 59.5% and males 57.5 %. The overall correct sex estimation was achieved in 58.5% of the cases. The predictive accuracy or assessment was higher for females compared to males. Consequently, the posterior ramus of mandible or mandibular ramus flexure can be considered as supplementary rather than a definitive means of sex determination. Hence, it is preferable to include as many parameters as possible to attain optimal accuracy.


Subject(s)
Asian People , Mandible , Sex Determination by Skeleton , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Dental Occlusion , Mandible/diagnostic imaging , Polymers , Retrospective Studies , Sex Determination by Skeleton/methods
3.
Bone Joint J ; 101-B(7_Supple_C): 98-103, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31256646

ABSTRACT

AIMS: The aim of this study was to determine the general postoperative opioid consumption and rate of appropriate disposal of excess opioid prescriptions in patients undergoing primary unilateral total knee arthroplasty (TKA). PATIENTS AND METHODS: In total, 112 patients undergoing surgery with one of eight arthroplasty surgeons at a single specialty hospital were prospectively enrolled. Three patients were excluded for undergoing secondary procedures within six weeks. Daily pain levels and opioid consumption, quantity, and disposal patterns for leftover medications were collected for six weeks following surgery using a text-messaging platform. RESULTS: Overall, 103 of 109 patients (94.5%) completed the daily short message service (SMS) surveys. The mean oral morphine equivalents (OME) consumed during the six weeks post-surgery were 639.6 mg (sd 323.7; 20 to 1616) corresponding to 85.3 tablets of 5 mg oxycodone per patient. A total of 66 patients (64.1%) had stopped taking opioids within six weeks of surgery and had the mean equivalent of 18 oxycodone 5 mg tablets remaining. Only 17 patients (25.7%) appropriately disposed of leftover medications. CONCLUSION: These prospectively collected data provide a benchmark for general opioid consumption after uncomplicated primary unilateral TKA. Many patients are prescribed more opioids than they require, and leftover medication is infrequently disposed of appropriately, which increases the risk for illicit diversion. Cite this article: Bone Joint J 2019;101-B(7 Supple C):98-103.


Subject(s)
Analgesics, Opioid/therapeutic use , Arthroplasty, Replacement, Knee/adverse effects , Pain Management/methods , Pain, Postoperative/prevention & control , Practice Patterns, Physicians' , Aged , Aged, 80 and over , Drug Prescriptions/statistics & numerical data , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Pain, Postoperative/epidemiology , Prospective Studies , Surveys and Questionnaires , United States/epidemiology
5.
Indian J Endocrinol Metab ; 18(6): 821-5, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25364677

ABSTRACT

CONTEXT: It is evident that about 30-50% of patients with Vitamin D deficiency (VDD) do not manifest develop secondary hyperparathyroidism (SHPT). A number of theories have been proposed to explain this lack of SHPT, including hypomagnesemia. SETTINGS AND DESIGN: Retrospective review of laboratory database. MATERIALS AND METHODS: We evaluated the differences in serum magnesium (Mg) levels among those with VDD with or without SHPT. A retrospective review of 6255 laboratory data of bone mineral profiles performed in the period of 2007-2013. After excluding patients with hypercalcemia, renal dysfunction/unknown kidney function and primary hypothyroidism, the remaining 1323 patient data were analyzed. SHPT was defined as serum parathyroid hormone >65 in those with VDD. STATISTICAL ANALYSIS USED: ANOVA and Wilcoxon tests as appropriate to compare means. Multivariate logistic regression to analyze relation between variables and outcome of SHPT. RESULTS: We noted that 55% patients (n = 727) had VDD, and among those who had VDD, 23% (n = 170) were hypocalcemic (corrected serum calcium <8.5). Patients with VDD who did not exhibit SHPT were 56% (n = 407). The mean (±standard deviation) serum Mg levels in the entire cohort (n = 1323) was 1.94 ± 0.26 mg/dl and 1.95 ± 0.26 mg/dl in VDD cohort and 2 ± 0.31 mg/dl in the VDD-hypocalcemic cohort. There was no statistical difference in the Mg levels among those with SHPT compared to those without SHPT (P = 0.14). Serum calcium and phosphorus were lower in those with SHPT (P = 0.06 and P < 0.001, respectively). In multivariate logistic regression, serum calcium (P = 0.043), phosphorus (P < 0.001) and severe VDD (P < 0.001) independently correlated with occurrence of SHPT in VDD. CONCLUSIONS: Serum Mg levels did not explain the functional hypoparathyroidism seen in about half of the patients with VDD. A low normal serum calcium and phosphorus levels are more likely to be associated with VDD patients who develop SHPT.

6.
Mycopathologia ; 176(3-4): 225-32, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23813152

ABSTRACT

Fungal infections of foot in patients with diabetes are not uncommon; however, foot infection due to Fusarium species has been rarely reported. We report here a case of a 50-year-old male with type 2 diabetes who developed multiple spontaneous nodular lesions on right foot without any systemic symptoms and signs for 6 months. The lesions were unresponsive to broad-spectrum antibacterial treatment. Fine needle aspiration cytology of nodular lesions revealed the presence of fungal hyphae, and Fusarium species was isolated from the same sample which was identified as Fusarium solani species complex: Fusarium falciforme. Radiological investigations and blood culture ruled out any dissemination of the disease. The lesions healed after voriconazole therapy for 3 months. No relapse was noted at the end of the next 6-month follow-up. All reported cases of Fusarium infection of foot in patients with diabetes in English and non-English literature since 1970 have been reviewed.


Subject(s)
Diabetes Complications/diagnosis , Diabetes Complications/pathology , Diabetes Mellitus, Type 2/complications , Foot/pathology , Fusariosis/diagnosis , Fusariosis/pathology , Fusarium/isolation & purification , Antifungal Agents/therapeutic use , Biopsy, Fine-Needle , Foot/microbiology , Fusarium/classification , Humans , Male , Middle Aged , Pyrimidines/therapeutic use , Triazoles/therapeutic use , Voriconazole
7.
Indian J Endocrinol Metab ; 16(3): 469-71, 2012 May.
Article in English | MEDLINE | ID: mdl-22629525

ABSTRACT

Adrenal incidentalomas of more than 4 cm size are usually malignant. We describe a 28-year-old woman with a 7-cm, non-functioning, well-demarcated adrenal mass, which was identified as an oncocytoma on histopathological examination. Therefore, a large, non-functioning, unilateral adrenal mass with preserved tumor outline should invoke the suspicion of oncocytoma, which is invariably a benign tumor.

8.
Rheumatol Int ; 31(12): 1561-5, 2011 Dec.
Article in English | MEDLINE | ID: mdl-20490806

ABSTRACT

The objective of the present study is to compare and quantify the postural differences and joint pain distribution between subjects with benign joint hypermobility syndrome (BJHS) and the normal population. This observational, non-randomized, and controlled study was conducted at Rheumatology and Physical Medicine and Rehabilitation Medicine Departments of a tertiary care teaching hospital. Subjects comprise 35 persons with diagnosis of BJHS, and the control group was matched for age and sex. Reedco's Posture score (RPS) and visual analogue scale (VAS) were the outcome measures. The subjects were assessed for pain in ten major joints and rated on a VAS. A standard posture assessment was conducted using the Reedco's Posture score. The same procedure was executed for an age- and sex-matched control group. Mean RPS for the BJHS group was 55.29 ± 8.15 and for the normal group it was 67 ± 11.94. The most common postural deviances in subjects with BJHS were identified in the following areas of head, hip (Sagittal plane), upper back, trunk, and lower back (Coronal plane). Intensity of pain was found to be more in BJHS persons than that of the normal persons, and the knee joints were the most affected. The present study compared and quantified the postural abnormalities and the pain in BJHS persons. The need for postural re-education and specific assessment and training for the most affected joints are discussed. There is a significant difference in posture between subjects with BJHS and the normal population. BJHS persons need special attention to their posture re-education during physiotherapy sessions to reduce long-term detrimental effects on the musculoskeletal system.


Subject(s)
Joint Instability/physiopathology , Pain/physiopathology , Postural Balance/physiology , Adolescent , Adult , Child , Female , Humans , Joint Instability/therapy , Knee Injuries/therapy , Knee Joint/physiopathology , Male , Pain Measurement , Physical Therapy Modalities , Young Adult
9.
Acta Neurol Scand ; 124(3): 211-4, 2011 Sep.
Article in English | MEDLINE | ID: mdl-20969559

ABSTRACT

OBJECTIVE: To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson's disease (PD). MATERIALS AND METHODS: Records of 12 patients with PD who underwent GPi-DBS at our institution from 2002 to 2008 were matched by pre-operative PD medication doses and pre-operative motor Unified Parkinson's Disease Rating Scale (UPDRS) scores to 12 cases of STN-DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). RESULTS: GPi and STN groups had similar mean pre-operative LEDs and motor UPDRS scores. At 6 months post-DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post-operative 'medication off/stimulation on' motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). CONCLUSIONS: We conclude that in disease-matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.


Subject(s)
Deep Brain Stimulation/statistics & numerical data , Globus Pallidus/physiology , Levodopa/administration & dosage , Parkinson Disease/drug therapy , Parkinson Disease/surgery , Subthalamic Nucleus/physiology , Aged , Antiparkinson Agents/administration & dosage , Deep Brain Stimulation/methods , Humans , Longitudinal Studies , Middle Aged , Neural Pathways/drug effects , Neural Pathways/physiopathology , Neural Pathways/surgery , Parkinson Disease/physiopathology , Retrospective Studies , Time , Treatment Outcome
10.
Br J Cancer ; 99(10): 1748-53, 2008 Nov 18.
Article in English | MEDLINE | ID: mdl-18841155

ABSTRACT

Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with > or =2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either 'classic' (> or =5 microliths) or 'limited' (<5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P=0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P=0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT.


Subject(s)
Lithiasis/epidemiology , Neoplasms, Germ Cell and Embryonal/epidemiology , Testicular Diseases/epidemiology , Testicular Neoplasms/epidemiology , Adult , Comorbidity , Family , Humans , Male , Prevalence
11.
Ann Oncol ; 17(11): 1615-9, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16600983

ABSTRACT

Peritoneal mesothelioma is a rare cancer of the peritoneum with about 250 new cases diagnosed each year in the United States. It is the second most common site for mesothelioma development and accounts for 10-20% of all mesotheliomas diagnosed in the United States. A meeting sponsored by the NIH Office of Rare Diseases was held in Bethesda, Maryland on September 13 and 14, 2004. The objective of this meeting was to review the epidemiology, biology and current surgical and medical management of peritoneal mesothelioma. In addition, the meeting also discussed clinical and pre-clinical evaluation of novel treatments for mesothelioma as well as ongoing laboratory research to better understand this disease. This report summarizes the proceedings of the meeting as well as directions for future clinical and basic research.


Subject(s)
Mesothelioma/pathology , Mesothelioma/therapy , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Clinical Trials as Topic , Drug Evaluation, Preclinical , Humans , Mesothelioma/epidemiology , Mesothelioma/genetics , National Institutes of Health (U.S.) , Peritoneal Neoplasms/epidemiology , Peritoneal Neoplasms/genetics , United States
12.
J Membr Biol ; 204(1): 33-8, 2005 Mar.
Article in English | MEDLINE | ID: mdl-16007501

ABSTRACT

A chemically synthesized peptide consisting of the C-terminus of the M protein of the Dengue virus type 1 strain Singapore S275/90 (DVM-C) produced ion channel activity in artificial lipid bilayers. The channels had a variable conductance and were more permeable to sodium and potassium ions than to chloride ions and more permeable to chloride ions than to calcium ions. Hexamethylene amiloride (100 microM) and amantadine (10 microM), blocked channels formed by DVM-C. Ion channels may play an important role in the life cycle of many viruses and drugs that block these channels may prove to be useful antiviral agents.


Subject(s)
Amiloride/analogs & derivatives , Dengue Virus/chemistry , Ion Channels/chemistry , Membranes, Artificial , Peptides/chemistry , Viral Matrix Proteins/chemistry , Amantadine/pharmacology , Amiloride/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Dengue Virus/physiology , Peptides/metabolism , Viral Matrix Proteins/antagonists & inhibitors , Viral Matrix Proteins/metabolism
13.
Cell Death Differ ; 12 Suppl 1: 962-70, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15832179

ABSTRACT

The destruction of CD4(+) T cells and eventual induction of immunodeficiency is a hallmark of the human immunodeficiency virus type 1 infection (HIV-1). However, the mechanism of this destruction remains unresolved. Several auxiliary proteins have been proposed to play a role in this aspect of HIV pathogenesis including a 14 kDa protein named viral protein R (Vpr). Vpr has been implicated in the regulation of various cellular functions including apoptosis, cell cycle arrest, differentiation, and immune suppression. However, the mechanism(s) involved in Vpr-mediated apoptosis remains unresolved, and several proposed mechanisms for these effects are under investigation. In this review, we discuss the possibility that some of these proposed pathways might converge to modulate Vpr's behavior. Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene.


Subject(s)
Apoptosis , CD4-Positive T-Lymphocytes/virology , Gene Products, vpr/physiology , HIV-1/physiology , Adaptor Proteins, Signal Transducing , Animals , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , COP9 Signalosome Complex , Carrier Proteins/physiology , Eukaryotic Initiation Factors/physiology , Gene Products, vpr/antagonists & inhibitors , Gene Products, vpr/pharmacology , HSP70 Heat-Shock Proteins/pharmacology , Humans , Intracellular Membranes/drug effects , Membrane Potentials/drug effects , Mitochondria/drug effects , Multiprotein Complexes/physiology , Peptide Hydrolases/physiology , Receptors, Glucocorticoid/drug effects , Signal Transduction/drug effects , vpr Gene Products, Human Immunodeficiency Virus
14.
Ann Oncol ; 15(9): 1366-72, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15319243

ABSTRACT

BACKGROUND: Apheresis catheters have simplified collection of peripheral blood stem cells (PBSC), but may be associated with thrombosis of the instrumented vessels. We performed a retrospective analysis to study the prevalence of thromboembolism associated with the use of femoral apheresis catheters in patients with breast cancer. PATIENTS AND METHODS: Patients were participants in clinical trials of high-dose chemotherapy with autologous PBSC rescue. They underwent mobilization with either high-dose cyclophosphamide (n = 21) or cyclophosphamide/paclitaxel (n = 64), followed by filgrastim. Double lumen catheters (12 or 13 Fr) were placed in the femoral vein and removed within 12 h of the last apheresis procedure. Apheresis was performed using a continuous flow cell separator and ACD-A anticoagulant. Thromboembolism was diagnosed by either venous ultrasonography or ventilation-perfusion scan. RESULTS: Nine of 85 patients (10.6%) undergoing large volume apheresis with use of a femoral catheter developed thromboembolic complications. Pulmonary embolus (PE) was diagnosed in five and femoral vein thrombosis in four patients. Four of the five patients who developed PE were symptomatic; one asymptomatic patient had a pleural-based, wedge-shaped lesion detected on a staging computed tomography scan. The mean number of apheresis procedures was 2.4 (range one to four) and the mean interval between removal of the apheresis catheter and diagnosis of thrombosis was 17.6 days. In contrast, none of 18 patients undergoing apheresis using jugular venous access and none of 54 healthy allogeneic donors undergoing concurrent filgrastim-mobilized PBSC donation (mean 1.7 procedures/donor) using femoral access experienced thromboembolic complications. CONCLUSIONS: Thromboembolism following femoral venous catheter placement for PBSC collection in patients with breast cancer may be more common than previously recognized. Healthy PBSC donors are not at the same risk. Onset of symptoms related to thrombosis tended to occur several weeks after catheter removal. This suggests that the physicians not only need to be vigilant during the period of apheresis, but also need to observe patients for thromboembolic complications after the catheter is removed. The long interval between the removal of apheresis catheter and the development of thromboembolism may have a potential impact on prophylactic strategies developed in future, such as the duration of prophylactic anticoagulation. Avoidance of the femoral site in breast cancer patients, and close prospective monitoring after catheter removal, are indicated.


Subject(s)
Blood Component Removal/adverse effects , Breast Neoplasms/therapy , Catheterization, Peripheral/adverse effects , Femoral Vein/surgery , Thromboembolism/etiology , Adolescent , Adult , Aged , Breast Neoplasms/complications , Female , Humans , Middle Aged , Retrospective Studies
15.
J Membr Biol ; 197(3): 135-43, 2004 Feb 01.
Article in English | MEDLINE | ID: mdl-15042345

ABSTRACT

The effects of site-directed mutations in NB, a protein encoded by the influenza B virus that has been shown to form cation-selective ion channels at pH 6.0, were studied on ion channel characteristics in artificial lipid bilayers. It was thought that the residues in the hydrophobic region of NB we selected for mutation might be involved in the transport of cations across the channel and that changes in these residues might affect channel properties such as gating and ion-selectivity. Serine residues at positions 20 and 28, threonine at position 24 and cysteine at position 26 were replaced by alanine. We found that the mutation S20A gave channels that did not gate and that remained open most of the time. Proton permeability of NB channels, as detected by fluorescence quenching, was also altered by the mutation S20A: channels were no longer proton-permeable. The other mutations, S28A, T24A and C26A, did not have any detectable effect on the activity or proton permeability of channels formed by NB. The results indicate that serine 20 may have an important role in normal function of NB channels.


Subject(s)
Ion Channel Gating , Ion Channels , Lipid Bilayers/chemistry , Membrane Potentials , Viral Proteins/chemistry , Amino Acid Substitution , Kinetics , Membranes, Artificial , Mutagenesis, Site-Directed , Recombinant Proteins/chemistry , Structure-Activity Relationship
16.
FEBS Lett ; 557(1-3): 99-103, 2004 Jan 16.
Article in English | MEDLINE | ID: mdl-14741348

ABSTRACT

A 63 residue peptide, p7, encoded by hepatitis C virus was synthesised and tested for ion channel activity in lipid bilayer membranes. Ion channels formed by p7 had a variable conductance: some channels had conductances as low as 14 pS. The reversal potential of currents flowing through the channels formed by p7 showed that they were permeable to potassium and sodium ions and less permeable to calcium ions. Addition of Ca(2+) to solutions made channels formed by p7 less potassium- or sodium-selective. Hexamethylene amiloride, a drug previously shown to block ion channels formed by Vpu encoded by HIV-1, blocked channels formed by p7. In view of the increasing number of peptides encoded by viruses that have been shown to form ion channels, it is suggested that ion channels may play an important role in the life cycle of many viruses and that drugs that block these channels may prove to be useful antiviral agents.


Subject(s)
Amiloride/analogs & derivatives , Amiloride/pharmacology , Ion Channels/biosynthesis , Lipid Bilayers , Viral Proteins/pharmacology , Amino Acid Sequence , Ion Channels/drug effects , Membrane Potentials/drug effects , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Viral Proteins/chemistry
17.
J Neurochem ; 82(2): 345-52, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12124435

ABSTRACT

Neuronal NMB cells were used to determine changes in gene expression upon treatment with dopamine. Twelve differentially expressed cDNAs were identified and cloned, one of them having 99.4% sequence homology with isoform 2 of a voltage-dependent anion channel (VDAC-2). The known role of VDAC, a mitochondrial outer-membrane protein, in transport of anions, pore formation, and release of cytochrome C prompted us to investigate the possible role of VDAC gene family in dopamine-induced apoptosis. Semi-quantitative PCR analysis indicated that expression of the three VDAC isoforms was reduced by dopamine. Immunoblotting with anti-VDAC antibodies detected two VDAC protein bands of 33 and 34 kDa. Dopamine decreased differentially the immunoreactivity of the 34 kDa protein. Whether the decrease in VDAC expression influence the mitochondrial membrane potential (Delta(Psi)(m)) was determined with the dye Rhodamine-123. Dopamine indeed decreased the mitochondrial Delta(Psi)(m), but the maximum effect was observed within 3 h, prior to the decrease in VDAC mRNA or protein levels. Cyclosporin A, a blocker of the mitochondrial pore complex, prevented the decrease in Delta(Psi)(m), but did not rescue the cells from dopamine toxicity. To elucidate possible involvement of protease caspases in dopamine-induced apoptosis, the effect of the caspase inhibitor z-Val-Ala-Asp(Ome)-FMK (zVAD) was determined. zVAD decreased dopamine toxicity, yet it did not rescue the mitochondrial Delta(Psi)(m) drop. Dopamine also decreased ATP levels. Finally, transfection of NMB cells with pcDNA-VDAC decreased the cytotoxic effect of dopamine. These findings are in agreement with the notion that the mitochondria, and VDAC, are important participants in dopamine-induced apoptosis.


Subject(s)
Apoptosis , Dopamine/pharmacology , Ion Channels/metabolism , Mitochondria/metabolism , Porins/metabolism , Adenosine Triphosphate/metabolism , Apoptosis/drug effects , Caspases/metabolism , Cell Line , Cell Survival/drug effects , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Enzyme Inhibitors/pharmacology , Gene Expression Profiling , Genes, Reporter , Humans , Intracellular Membranes/drug effects , Intracellular Membranes/physiology , Ion Channels/genetics , Membrane Potentials/drug effects , Mitochondrial Membrane Transport Proteins , Mitochondrial Permeability Transition Pore , Neurons/cytology , Neurons/drug effects , Neurons/metabolism , Porins/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Transfection , Voltage-Dependent Anion Channel 2 , Voltage-Dependent Anion Channels
19.
Diabetes Care ; 24(11): 1978-83, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11679468

ABSTRACT

OBJECTIVE: To determine whether insulin resistance and secretion differ in obese premenopausal African-American women with and without glucose intolerance. RESEARCH DESIGN AND METHODS: A total of 63 women underwent oral glucose tolerance tests (OGTTs). A total of 48 women underwent frequently sampled intravenous glucose tolerance tests (FSIGTs). Insulin resistance was determined from the insulin sensitivity index (S(I)) from the FSIGT. Insulin secretion during the OGTT was determined by (I(30 min) - I(0 min))/(G(30 min) - G(0 min)) and during the FSIGT by the acute insulin response to glucose (AIRg). The disposition index, the product of AIRg and S(I), was used to determine whether AIRg was adequate to compensate for insulin resistance. Statistical analyses included one-way analysis of variance with Bonferroni corrections for multiple comparisons and regression analyses. RESULTS: The women were divided into three groups: nonobese glucose tolerant (n = 32), obese glucose tolerant (n = 17), and obese glucose intolerant (n = 14). The BMI of the three groups were 24.8 +/- 2.3, 37.8 +/- 5.5, and 42.0 +/- 7.6 kg/m(2) (mean +/- SD), respectively (P < 0.0001). The ages of the three groups were 34.9 +/- 8.4, 32.1 +/- 5.0, and 41.1 +/- 6.3 years (P = 0.011). S(I) was higher in the nonobese women than in the obese glucose-tolerant women (3.99 +/- 1.44 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.03). S(I) was similar in the obese glucose-intolerant and obese glucose-tolerant women (2.12 +/- 1.27 vs. 2.66 +/- 2.14 l x mU(-1) x min(-1), P = 0.9). OGTT showed that insulin secretion was lower in the glucose-intolerant than the obese glucose-tolerant women (1.73 +/- 1.38 vs. 3.62 +/- 2.11, P = 0.005). FSIGT showed that AIRg was not significantly lower in glucose-intolerant than in obese glucose-tolerant women (807 +/- 665 vs. 1,253 +/- 655 mU x l(-1) x min, P = 0.078). The disposition index was lower in glucose-intolerant than in obese glucose-tolerant women (1,324 +/- 1,061 vs. 2,656 +/- 1,415, P = 0.014). CONCLUSIONS: Obese premenopausal African-American women with and without glucose intolerance have a similar degree of insulin resistance but differ in insulin secretion.


Subject(s)
Black People , Blood Glucose/metabolism , Glucose Intolerance/blood , Insulin Resistance/physiology , Insulin/metabolism , Islets of Langerhans/metabolism , Obesity/blood , Premenopause/physiology , Absorptiometry, Photon , Adipose Tissue/anatomy & histology , Adipose Tissue/diagnostic imaging , Black or African American , Body Composition , Female , Glucose Tolerance Test , Humans , Infusions, Intravenous , Insulin/administration & dosage , Insulin/blood , Insulin Secretion , Medical History Taking , National Institutes of Health (U.S.) , Organ Size , Physical Examination , Regression Analysis , Tomography, X-Ray Computed , United States
20.
Clin Cancer Res ; 7(7): 1888-93, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11448901

ABSTRACT

PURPOSE: Thalidomide is a potent teratogen that causes dysmelia in humans. Recently, in vitro data suggested that it inhibits angiogenesis. Prostate cancer is dependent on the recruitment of new blood vessels to grow and metastasize. Based on those data, we initiated a Phase II trial of thalidomide in patients with metastatic androgen-independent prostate cancer. EXPERIMENTAL DESIGN: This was an open-label, randomized Phase II study. Thalidomide was administered either at a dose of 200 mg/day (low-dose arm) or at an initial dose of 200 mg/day that escalated to 1200 mg/day (high-dose arm). RESULTS: A total of 63 patients were enrolled onto the study (50 patients on the low-dose arm and 13 patients on the high-dose arm). Serum prostate-specific antigen (PSA) decline of > or = 50% was noted in 18% of patients on the low-dose arm and in none of the patients on the high-dose arm. Four patients were maintained for > 150 days. The most prevalent complications were constipation, fatigue, neurocortical, and neurosensory. CONCLUSION: Thalidomide, an antiangiogenesis agent, has some activity in patients with metastatic prostate cancer who have failed multiple therapies. A total of 27% of all patients had a decline in PSA of > or = 40%, often associated with an improvement of clinical symptoms. Because our preclinical studies had shown that thalidomide increases PSA secretion, we believe that the magnitude of PSA decline seen in our trial justifies further study.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Prostatic Neoplasms/drug therapy , Thalidomide/therapeutic use , Aged , Aged, 80 and over , Androgens/physiology , Dose-Response Relationship, Drug , Endothelial Growth Factors/blood , Fibroblast Growth Factor 2/blood , Fibroblast Growth Factor 2/drug effects , Follow-Up Studies , Humans , Lymphokines/blood , Lymphokines/drug effects , Lymphotoxin-alpha/blood , Male , Middle Aged , Mood Disorders/chemically induced , Neovascularization, Pathologic/pathology , Neutropenia/chemically induced , Prostate-Specific Antigen/blood , Prostate-Specific Antigen/drug effects , Prostatic Neoplasms/blood supply , Prostatic Neoplasms/pathology , Survival Analysis , Time Factors , Treatment Outcome , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factors
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