Influence of alcohol consumption on oxidative stress and antioxidant status in cancer patients--case-control study from Western Nepal.

AIM: The present study assess the effect of consumption of alcohol on oxidative stress and antioxidant status in patients suffering from different types of cancer. METHODS: This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C, α-tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared. RESULTS: The TBARS level was found to be significantly higher (p≤0.001) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance (p≥0.05) was observed in the level of vitamin C and α-tocopherol. GSH and TAA level were significantly decreased (p≤0.001) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit. CONCLUSION: Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development.

Effects of cigarette smoking on lipid peroxidation and antioxidant status in cancer patients from Western Nepal.

OBJECTIVES: There is growing evidence that oxidative stress (OS) has a causal relationship with cancer and a weak antioxidant defense can aggravate it further. We therefore, undertook this study to examine lipid peroxidation (TBARS), total antioxidant activity (TAA), ascorbic acid (vitamin C) and α- tocopherol levels in cancer patients, with special attention to the influence of smoking. METHODS: The study subjects were 42 patients (61.19 ± 10.1 yrs) suffering from cancer and 43 normal subjects (NS) (56.69 ± 19.1 yrs). Plasma levels of TBARS, TAA, vitamin C and ?- tocopherol were estimated. RESULTS: TAA and α-tocopherol levels were significantly lower and TBARS levels significantly higher in cancer patients when compared to NS. In smoking cancer patient's ?-tocopherol levels were significantly low and TBARS significantly raised. CONCLUSION: Our observations indicate that increased lipid peroxidation, reduced total antioxidant activity and ?-tocopherol levels are associated with cancer development, with and without smoking. However, a greater reduction of TAA in smokers may be due to increased oxidants introduced by smoking.

A study of oxidative stress, antioxidant status and lipid profile in diabetic patient in the western region of Nepal.

AIMS AND OBJECTIVES: Diabetes mellitus (DM) is often termed as a disease of premature aging. Several studies have indicated lopsided redox balance due to pro oxidant environment as one of the important etiological factors. Some recent researches also indicate a causal relationship with oxidative stress (OS). So far, no study has been undertaken on this aspect in Nepali populations. We, therefore, aimed this maiden study in Nepali population to examine redox balance by measuring OS and antioxidant status along with lipid profile in 37 patients of DM type- 2 and 30 matched normal subjects. METHODOLOGY: Thirty seven patients of DM type-2 without any complications (mean age= 57.6+/- 10.6 years) and 30 normal subjects (mean age= 55.8 +/- 14.8 years) were included in this study. Body Mass Index (BMI) and Waist/Hip (W/H) ratio were measured. Fasting blood sample was collected for the analysis of total antioxidant activity (TAA), plasma and urinary thiobarbituric acid reactive substances (TBARS) and lipid profile by standard procedures in both the groups. The statistical analysis was done with SPSS 10 version. RESULTS: Total cholesterol, triglyceride, VLDL-cholesterol, LDL-cholesterol, plasma and urinary TBARS were significantly raised whereas, plasma TAA was significantly reduced in DM type-2 patients as compared to controls. The comparison of old and fresh cases revealed that though TAA was lower and PTBARS and UTBARS were higher in patients but did not attain the level of significance. W/H ratio is significantly higher in patients compared to normal subjects. But, no significant correlation of BMI and W/H with lipid profile is observed in both control and patients. CONCLUSION: Oxidative stress is raised in type 2 DM patients. This along with deranged lipid profile and decreased antioxidant status could be the risk factors in the development of complications associated with DM.

Right-sided hemiagenesis of the thyroid lobe and isthmus: A case report.

Unilateral or bilateral hypoplasia or agenesis of one or both thyroid lobes, with or without isthmic agenesis, is a rare developmental anomaly. Hemiagenesis of the left lobe is far commoner than of the right. Clinically, these patients may be euthyroid, hyperthyroid, or hypothyroid. Ultrasonography is usually able to diagnose this condition easily, as we demonstrate in this case report of a 37-year-old lady with an incidentally detected thyroid nodule who was found to have hemiagenesis of the right lobe and isthmus.

Need for an individualized and aggressive management of multinodular goiters of endemic zones by specially trained surgeons: experience in western Nepal.

BACKGROUND: The goals of the present study were to explore the presentation of multinodular goiter (MNG) and solitary thyroid nodules (STN) in the sub-Himalayan belt, including the risk of malignancy, and to evaluate whether specialized surgeon training in endocrine surgery has an effect on reducing complications. METHODS: This retrospective study (1998-2003) analyzed 624 patients with thyroid disorders seen in the thyroid clinic of a tertiary care hospital in western Nepal. The findings included 67.7% (n = 423: euthyroid, 297, toxic, 126) multinodular goiters (MNG) and 18.5% (n = 116) STN. Rest of patients of other thyroid disorders were excluded from the study. Ultrasonography and fine-needle aspiration cytology (FNAC) were the available diagnostic adjuncts. To evaluate the role of surgeon training, outcomes were compared between patients cared for by surgeons specially trained in endocrine surgery and those who were not. Prognostic markers indicated aggressiveness of cancers. RESULTS: Of the 539 MNG and STN patients in this series, 236 underwent operation. Of these, 25.7% (139/539) were toxic, and 11.31% had associated carcinoma. Aggressive cancers, like poorly differentiated (4.9%) and anaplastic types (18%), were more common than in series of patients from iodine-sufficient regions. Patients 40-55 years of age were more likely to have toxicity, and those > 60 years of age were more likely to have aggressive cancers. Postoperative complication rates were lower in the group treated by surgeons who had special training in endocrine surgery. CONCLUSIONS: There is a higher incidence of toxicity and malignancy in MNG in an endemic goiter zone. The limited diagnostic and therapeutic facilities in the region under study warrant a high degree of clinical suspicion and judgment, sound knowledge of thyroid physiology, thorough interpretation of hormone test results, and meticulous surgical techniques. The treatment must be individualized with consideration of humanitarian and socioeconomic factors, without compromising the quality of care and its long-term consequences. Aggressive management of malignancy and toxicity with total thyroidectomy is needed as primary therapy in many instances. However, subtotal excision is more useful in carefully selected cases with a small remnant. Specialized training in thyroid surgery appears to be valuable in reducing complications.

A perplexing case of gastrointestinal haemorrhage.

Choriocarcinoma is a gestational trophoblastic tumour with a high metastatic potential but presentation with gastrointestinal haemorrhage due to jejunal mucosal metastasis is very rare. A 25-year-old Nepali woman presented with severe anaemia and massive gastrointestinal haemorrhage after normal pregnancy following evacuation of a hydatiform mole. During laparotomy, the patient was found to have extensive jejunal mucosal metastases.

Vitamin C status in cancer patients and healthy subjects from the local population of Pokhara.

OBJECTIVES: To assess vitamin C status by determining plasma ascorbic acid level in 55 cancer patients and 55 matched normal subjects serving as control. METHODS: The proven cancer patients were selected from those attending Manipal Teaching Hospital, Pokhara. Matched controls were from the staff of Manipal Teaching Hospital or attendants of the patients. Plasma ascorbic acid was determined by the method of Natelson. Unpaired student 't' test was used for the statistical evaluation. Statistical analysis was done by SPSS version 9 software. RESULTS: The mean level of vitamin C in normal subjects and patients was 1.03+/-0.26 mg/dl and 0.90+/-0.30 mg/dl respectively. None of the subjects in either group had deficient status (<0.2 mg/dl). Although its status was normal in both the groups but patients had lower level than normal subjects. Smokers and alcohol consumers had significantly lower level than non-smoker and non-alcoholics. CONCLUSION: In the local population, vitamin C deficiency is not an etiologic factor in malignancy. Smoking and alcohol adversely affects the status of this vitamin.

Electrical stimulation of the auditory nerve: single neuron strength-duration functions in deafened animals.

Destruction of cochlear hair cells initiates degenerative changes within auditory nerve fibres (ANFs), including loss of peripheral processes and demyelination of the cell body. These changes are likely to affect the biophysical processes involved in action potential generation to an electrical stimulus. We measured the strength-duration relationship in acutely deafened (100% ANF survival) versus long-term deafened cochleae (approximately 15% ANF survival) by recording from single neurons in the central nucleus of the inferior colliculus (ICC). Input/output functions were constructed for 22 ICC neurons in response to stimulation of the auditory nerve using biphasic current pulses of 20-1000 micros/phase. Strength-duration curves were derived and found to be of the same general form for both acute and long-term deafened cochleae. While there was an increase in rheobase for neurons from long-term versus acute deafened cochleae, this increase was not statistically significant (p=0.097). In contrast, chronaxie--which is related to the membrane time constant--was significantly shorter in the long-term deafened cochleae (p = 0.004). This presumably reflects a shift in the site of action potential initiation to the larger diameter, heavily myelinated central axon as a result of the pathology. These changes in the site of action potential generation have implications for the delivery of charge to ANFs via cochlear implants.

Energetics of rat papillary muscle during contractions with sinusoidal length changes.

The mechanical efficiency of rat cardiac muscle was determined using a contraction protocol involving cyclical, sinusoidal length changes and phasic stimulation at physiological frequencies (1-4 Hz). Experiments were performed in vitro (27 degrees C) using rat left ventricular papillary muscles. Efficiency was determined from measurements of the net work performed and enthalpy produced by muscles during a series of 40 contractions. Net mechanical efficiency was defined as the percentage of the total, suprabasal enthalpy output that appeared as mechanical work. Maximum efficiency was approximately 15% at contraction frequencies between 2 and 2.5 Hz. At lower and higher frequencies, efficiency was approximately 10%. Enthalpy output per cycle was independent of cycle frequency at all but the highest frequency used. The basis of the high efficiency between 2 and 2.5 Hz was that work output was also greatest at these frequencies. At these frequencies, the duration of the applied length change was well matched to the kinetics of force generation, and active force generation occurred throughout the shortening period.

Response of inferior colliculus neurons to electrical stimulation of the auditory nerve in neonatally deafened cats.

Response properties of neurons in the inferior colliculus (IC) were examined in control and profoundly deafened animals to electrical stimulation of the auditory nerve. Seven adult cats were used: two controls; four neonatally deafened (2 bilaterally, 2 unilaterally); and one long-term bilaterally deaf cat. All control cochleae were deafened immediately before recording to avoid electrophonic activation of hair cells. Histological analysis of neonatally deafened cochleae showed no evidence of hair cells and a moderate to severe spiral ganglion cell loss, whereas the long-term deaf animal had only 1-2% ganglion cell survival. Under barbiturate anesthesia, scala tympani electrodes were implanted bilaterally and the auditory nerve electrically stimulated using 100 micros/phase biphasic current pulses. Single-unit (n = 419) recordings were made through the lateral (LN) and central (ICC) nuclei of the IC; responses could be elicited readily in all animals. Approximately 80% of cells responded to contralateral stimulation, whereas nearly 75% showed an excitatory response to ipsilateral stimulation. Most units showed a monotonic increase in spike probability and reduction in latency and jitter with increasing current. Nonmonotonic activity was seen in 15% of units regardless of hearing status. Neurons in the LN exhibited longer latencies (10-25 ms) compared with those in the ICC (5-8 ms). There was a deafness-induced increase in latency, jitter, and dynamic range; the extent of these changes was related to duration of deafness. The ICC maintained a rudimentary cochleotopic organization in all neonatally deafened animals, suggesting that this organization is laid down during development in the absence of normal afferent input. Temporal resolution of IC neurons was reduced significantly in neonatal bilaterally deafened animals compared with acutely deafened controls, whereas neonatal unilaterally deafened animals showed no reduction. It would appear that monaural afferent input is sufficient to maintain normal levels of temporal resolution in auditory midbrain neurons. These experiments have shown that many of the basic response properties are similar across animals with a wide range of auditory experience. However, important differences were identified, including increased response latencies and temporal jitter, and reduced levels of temporal resolution.