Determinants of oxidative stress and DNA damage (8-OhdG) in squamous cell carcinoma of head and neck.

Background: Squamous cell carcinoma of head and neck (SCCHN) is a major concern of health risk in developing countries, such as India. Apart from genetic configuration, environmental and lifestyle factors, as well as poor oral hygiene, provide free radical-generating environment, which may contribute to the development of cancer through DNA damage. Materials and Methods: Here we ascertained the various oxidative stress determinants in diagnosed SCCHN patients with health risk addictions. This study further evaluated the incremental effects inflicted by these lifestyle factors on redox status. The study included 100 consenting SCCHN patients and 90 matched healthy controls. Salivary total antioxidant capacity (TAC), glutathione (GSH), free radicals: such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) along with oxidative DNA adduct (8-OHdG) were monitored. Results: Our findings indicated altered salivary oxidant-antioxidant status in SCCHN. A substantial rise in ROS (~2.0 folds) and RNS (~1.4 folds), together with significant lowering in TAC (~1.2 folds) and GSH (~1.7 folds) was observed. The 8-OHdG levels were also found to be considerably higher (P < 0.001) in salivary cell's DNA of these patients. Conclusions: Our results demonstrate significant redox imbalance in cancer patients suggesting their paramount importance in the development of SCCHN.

Association and treatment response to capecitabine-based chemoradiotherapy with CYP2C9 polymorphism in head and neck cancer.

Aims : The aim of the present study is to investigate the association of polymorphism in cytochrome P450 2C9 (CYP2C9) with head and neck squamous cell carcinoma (HNSCC) and response in patients receiving chemoradiotherapy. Materials and Methods : One hundred ten males suffering from locally advanced head and neck squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9*2 and CYP2C9*3, leading to poor metabolizers (PMs) by PCR-based RFLP. Each case was assessed thoroughly for treatment response following WHO criteria. Results : The frequency of heterozygous genotypes of both CYP2C9*2 (27.3%) and CYP2C9*3 (20.1%) were found to be significantly higher in the HNSCC cases as compared to the healthy controls. Tobacco intake in the form of chewing or smoking and alcohol intake resulted in several fold increase in the risk to HNSCC in the cases carrying variant genotypes of CYP2C9*2 or CYP2C9*3. Further, majority of the cases assessed for response (134) carrying variant alleles of both CYP2C9*2 (65.3%) or CYP2C9*3 (70.58%) were found to respond poorly to the radio-chemotherapy. Conclusions : The data suggests a significant association of the CYP2C9 polymorphism with HNSCC and treatment outcome underlining the importance of pretherapeutic genotyping in determining the treatment schedule.

Continuous hyperfractionated accelerated radiotherapy in advanced head and neck malignancies.

58 patients of advanced head and neck cancer were treated by continuous hyperfractionated accelerated radiotherapy (study group) or conventional radiotherapy (control group). The study group of 29 patients had 26/29 (89%) of patients of stage T3 and T4 with 12/29 (41% 0) > N2 disease. The schedule employed was 1.5 Gy 3 times a day in 36 fractions on 12 treatment days without stopping for weekends. The spinal dose has been kept at 40.5 Gy and interfraction interval has been strictly kept at 6 hrs. Clinical, as well as radiological assessment has been encouraging with 23/29 (79.13%) of patients achieving complete regression of the primary tumor and nodal disease. Compared to the conventionally treated controls this value has been significant (P value < 0.001). In stage III disease tumor control has been in 9/10 (90%) cases, while in stage IV disease in 14/19 (73.68%) cases. The acute mucosal reactions have been found to be severe in these cases with 18/29 i.e. 62.06% suffering from grade III reactions. Nasogastric feeding was required in 25.92% of patients.

Effect of Prunus amygdalus seeds on lipid profile.

The effect of Prunus amygdalus, which is rich in unsaturated fat, fibre diet and low cholesterol was studied in 36 normolipidemic male albino rabbits for 60 days. Three different doses i.e. whole seeds defatted and oil showed a decrease in serum total cholesterol, triglyceride, LDL cholesterol, VLDL cholesterol and an increase in phospholipid, faecal sterol and HDL cholesterol. The maximum effects where shown by whole seeds followed by oil and defatted.

Changes in the blood lipid profile after administration of Ocimum sanctum (Tulsi) leaves in the normal albino rabbits.

Administration of fresh leaves of Ocimum sanctum (Tulsi) mixed as 1 g and 2 g in 100 gms of diet given for four weeks, brought about significant changes in the lipid profile of normal albino rabbits. This resulted in significant lowering in serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and significant increase in the HDL-cholesterol and total faecal sterol contents.

Effect of alcohol on serum lipids & lipoproteins in male drinkers.

The evaluation of the effect of moderate and high doses of ethanol on the serum levels of triglyceride (TG), total cholesterol (TC), cholesterol content of very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL), HDL2, HDL3 subfractions and apoproteins: apo-AI and apo-B was undertaken in 45 (25 controls, 10 moderate and 10 high dose drinkers) healthy males. The results of this preliminary study showed a significant rise in total HDL-cholesterol and apo-AI levels of alcoholics of both the groups. Out of the two subfractions, HDL2 appeared to be induced more. Increased levels of atherogenic lipids (TG, VLDL-chol., LDL-chol. and apo-B) were found in high as well as moderate drinkers. Our results suggest that the benefit of alcohol intake need to be weighed carefully against its considerable risks.

Computed tomography of brain in symptomatic birth asphyxia.

Twenty five asphyxiated newborns (seventeen term and eight preterm) with mean gestational age of 37 weeks (range 28-48 weeks) and mean birth weight of 2.4 kg (range 0.75 kg to 3.5 kg), respectively, constituted the cases in present study. Normal CT scan was found in five term (29.4%) and two preterm babies (25%). CT abnormalities noted in term babies included hemorrhage (subarachnoid 5.8%, intracerebral 11.6%), hypodensity (mild 23.2%, moderate 11.6% severe 5.8%); hypodensity with hemorrhage 5.8% and cerebral atrophy 5.8%. In the preterm babies abnormalities included intraventricular hemorrhage in 25%, isolated hypodensity in 37.5% and hypodensity with hemorrhage in 12.5% cases. Where as mild hypodensity on CT scan in the absence of hemorrhage or other gross abnormality was indicative of a favourable outcome, moderate to severe hypodensity was indicative of ischemic brain injury and an unfavourable outcome. The presence of intraventricular hemorrhage irrespective of the size of bleed was associated with mortality in all in the present study.

Japanese B encephalitis with neurocysticercosis.

A case of Japanese encephalitis (JE) with multiple calcified lesions suggestive of calcified neurocysticercosis on CT scan of the head is reported. The presence of nonenhancing calcified lesions and rising antibody titres for JE differentiated it from acute encephalitis neurocysticercosis. Post mortem studies indicate that neurocysticercosis predisposes to fatal JE infection. The present report is of an association of the two diseases which did not result in a fatal outcome.