Kafil Akhtar

Influence of ellagic acid on prostate cancer cell proliferation: A caspase–dependent pathway

OBJECTIVE To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells. METHODS Ellagic acid (10-100 mol/L) treatment (48 h) of human prostate carcinoma PC3 cells was found to result in a dose-dependent inhibition of cell growth and apoptosis of PC3 cells as assessed by MTT assay, western blotting, flow cytometry and confocal microscopy. RESULTS We observed that ellagic acid treatment of PC3 cells resulted in a dose dependent inhibition of cell growth/cell viability. This ellagic acid caused cell growth inhibition was found to be accompanied by induction of apoptosis, as assessed by the cleavage of poly (ADP-ribose) polymerase (PARP) and morphological changes. Further, induction of apoptosis accompanied a decrease in the levels of antiapoptotic protein Bcl-2 and increase in proapoptotic protein Bax, thus shifting the Bax: Bcl-2 ratio in favor of apoptosis. Ellagic acid treatment of PC3 cells was also found to result in significant activation of caspases, as shown by the dose dependent decrease in the protein expression of procaspase-3, -6, -8 and -9. This ellagic acid-mediated induction of apoptosis was significantly (80%-90%) inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethylketone (Z-VAD-FMK). Thus these data suggested an essential role of caspases in ellagic acid-mediated apoptosis of PC3 cells. CONCLUSIONS It is tempting to suggest that consumption of tropical pigmented fruits and vegetables could be an effective strategy to combat prostate cancer.

Primary neuroendocrine carcinoma of the breast

Primary neuroendocrine carcinoma of the breast is rare-only about 30 cases have been reported in literature. Immunohistochemical examination showing expression of chromogranin and/or synaptophysin confirms evidence of neuroendocrine differentiation. Usually foci of neuroendocrine differentiation can be seen in breast carcinoma and are reported to be present in about 2-5% of breast cancer cases. Here, we report a case of breast carcinoma in which most of the areas studied on the tissue section showed neuroendocrine differentiation.

In vivo induction of antioxidant response and oxidative stress associated with genotoxicity and histopathological alteration in two commercial fish species due to heavy metals exposure in northern India (Kali) river.

Heavy metals can significantly bioaccumulate in fish tissues. The step wise mechanism of heavy metal toxicities on fish health is still limited. The present study assessed the tissue-specific antioxidant response and oxidative stress biomarkers of commercially important fish species namely, Channa striatus and Heteropneustes fossilis inhabiting Kali River of northern India where heavy-metal load is beyond the World Health Organisation - maximum permissible limits. Heavy metals chromium (Cr), nickel (Ni), lead (Pb) and cadmium (Cd) were elevated in both fish species compared to recommended values of the Federal Environmental Protection Agency (FEPA), 1999 for edible fishes. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CATA) activities in all tissues (brachial, neural, renal and hepatic) were altered. Cellular lipid and protein compromisation in both fishes induced by heavy metals was determined by lipid peroxidation (LPO) and protein carbonylation (PC) assays. Micronucleus (MN) test of erythrocytes and comet assay of liver cells confirmed genotoxicity. Histopathology of the liver, kidney and brain of affected fishes was distorted significantly with its reference fishes thereby affecting the quality and quantity of these fish stocks. This raises a serious concern as these fishes are consumed by the local population which would ultimately affect human health.

Dysgerminoma with Pregnancy and Viable Baby: A Case Report

Dysgerminomas are the most common of primitive germ cell tumors of the ovary, accounting for 1-5% of all ovarian malignancies. The reproductive age group females are most commonly affected, thereby causing problems in conception and if pregnancy occurs, it leads to feto-maternal compromise. It is extremely rare to have a successful natural pregnancy, with viable child birth with a coexisting dysgerminoma, without any assisted reproductive interventions. We hereby report a case of successful spontaneous natural pregnancy in a primi gravida, associated with dysgerminoma, with no feto-maternal compromise.

Ultrasound guided fine needle aspiration biopsy of retroperitoneal masses

The study was undertaken to evaluate the reliability of ultrasound guided fine needle aspiration biopsy (FNAB) in distinguishing benign and malignant lesions in the retroperitoneum and correlate the diagnosis by cytology of retroperitoneal masses with the results obtained by histology. The clinicopathological study was carried out in 50 patients presenting with retroperitoneal masses on ultrasonography. Fine needle aspiration under ultrasound guidance of these masses was performed by 20-22G needle after thorough clinical examination. Malignant lesion constituted the maximum number of cases - 31 (62%) followed by benign and inflammatory lesion - 16 cases (32%). Eleven cases out of 23 renal masses were Wilms tumour, 4 were renal cell carcinoma and there was a single case of angiomyolipoma of kidney. Out of 20 cases with retroperitoneal lymphadenopathy 12 cases (60%) were inflammatory, mainly tuberculosis and 8 (40%) had malignancy. Out of the 7 cases of miscellaneous retroperitoneal masses, 3 were fibrohistiocytic tumour and 2 were myxoid liposarcoma. Ultrasound guided FNAB is an inexpensive, rapid, safe and accurate procedure for the diagnosis of retroperitoneal masses.

Paraganglioma of the thyroid gland: cytologists' enigma.

Paraganglioma is a neuroendocrine tumour derived from extra-adrenal cells of the neural crest paraganglia of the autonomic nervous system. These rare neoplasms comprise of around 0.012% of head and neck tumours. Paraganglioma arising in the thyroid gland is exceptionally uncommon and can present as a diagnostic challenge on fine-needle aspiration cytology (FNAC). We report a case of primary thyroid paraganglioma in a 19-year-old woman who presented with a solitary thyroid nodule without palpable cervical lymphadenopathy. FNAC from the lesion caused diagnostic dilemma by mimicking follicular neoplasm and C-cell-derived thyroid tumours; final diagnosis was established by histopathology and immunohistochemistry. The main purpose of this case report is to discuss the differential diagnosis and emphasise on the need of immune markers in the diagnosis of thyroid paraganglioma. In view of the uncertain malignant potential of these tumours, a long-term follow-up is recommended.

Prevalence of hepatitis C virus in Aligarh: A seven year experience

Sir, Blood transfusion is life saving, but the chances of transmission of microorganisms remain a potential danger. With proper selection of donors on the basis of detailed clinical history and examination, along with the availability of a sophisticated screening procedure, the chances of transmission of diseases through transfusion have reduced considerably. However, the risk is only minimized and not ruled out. Hepatitis C virus (HCV), the main etiological agent of the clinical entity, formerly known as Non-A, Non-B Hepatitis, was discovered in 1989 by Choo et al.(1) HCV along with Hepatitis B virus (HBV) is responsible for the majority of post-transfusion hepatitis. The present study was done to determine the prevalence rate of HCV antibodies in replacement and voluntary donors attending the Blood Bank of the Jawaharlal Nehru Medical College Hospital, A.M.U., Aligarh, over a period of seven years, from January 2001 to December 2007. Out of 68173 donors, there were 44984 replacement donors and 23189 voluntary donors. No honorary or professional donor was bled. Thereafter, 5 – 10 ml of blood was withdrawn with a 10 ml syringe and subjected to anti-HCV testing, using a commercially available third generation anti-HCV ELISA kit. A majority of the donors were young males in the age group of 30 – 40 years (60%), followed by 30% donors in the age group of 21 – 30 years. HCV positive cases among the apparently healthy blood donors were assessed. In the year 2001; there was no donor who showed positivity for HCV antibody. In the year 2002, there was only one positive case per 8130 donations (0.01%). The year 2003 showed an increase in the number of positive cases for HCV, three positive cases per 9577 donations (0.03%). The year 2004 showed a further increase, with eight positive cases per 10842 donations (0.07%). The scenario in 2005 was somewhat similar to that seen in 2003, with five positive cases per 10990 donations (0.04%). There was a steep rise in 2006, with 13 positive cases per 11068 donations (0.12%). The number of positive cases continued to rise in 2007, with 18 positive cases per 11566 donations (0.15%). A majority of the positive cases belonged to the age group 21 – 30 years, 22 in total (45.83%), followed by 14 cases (29.16%) in the age group 31 – 40 years. There were seven cases (14.58%) in the second decade, while only five positive cases (10.41%) were seen in the fifth decade. The study revealed only three female positive cases out of a total of 48 positive cases (6.25%) during the entire period of study. One reason for this data could be the overall low number of female donors as compared to male donors. Transfusion-associated infections continue to be a big threat to the safety of blood supply, moreso in the developing and underdeveloped countries. Viral infections are the major cause of morbidity and mortality in blood recipients and a majority of transfusion-associated hepatitis is caused by the Hepatitis C virus. With approximately 170 million people worldwide estimated to be infected with HCV, a figure that is four times the HIV infection status, it has the potential to be the next pandemic.(2) The present study was undertaken to determine the prevalence of HCV antibodies in healthy blood donors. The presence of anti-HCV does not constitute a diagnosis of Hepatitis C, but may be indicative of recent and/or past infection by hepatitis C virus. A nonreactive test result does not exclude the possibility of exposure to HCV. Levels of anti-HCV may be undetectable in early infections due to a low titer; polymerase chain reaction (PCR) may play an important role under such circumstances. Even then, screening blood donors for anti-HCV has reduced the incidence of post-transfusion non-A and non-B hepatitis dramatically. Hepatitis C virus (HCV) is a hepatotropic virus of family Flaviviridae and genus Hepacivirus, having a single standard RNA of positive polarity as genomic material. A large number of genotypes have been identified among hepatitis C virus isolates from all over the world. Presently six main groups of sequence variants have been characterized, corresponding to types 1 – 6; each group containing a number of more closely related subtypes (a, b, c, etc.).(3) Genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India, and is associated with significant hepatic steatosis and fibrosis.(4) The safety of blood transfusion is compromised in India due to its dependence on replacement donors, endemic hepatitis in this region, high cost of screening, and a lack of funds and trained personnel. Williams et al., in 1992, conducted a study and showed a seroprevalence of 11.1% for antibodies to HCV in multiple transfused thalassemia major patients.(5) This high prevalence could have been because of improper clinical examination and screening of the donors. However, proper pre-donation screening of donors and rejecting volunteers with a past history of viral hepatitis has shown a lower prevalence of post-transfusion Hepatitis C infection (0.07%) in our study, as compared to a higher prevalence of 2.0% reported by Kothari et al.(6) Our study showed an alarming percentage of HCV positive cases in the younger generation, 36 cases (74.9%), with an upward trend of positivity, with time. Routine HCV antibody screening and proper clinical examination should be carried out in blood donors with a thrust toward youth surveillance, which will aid in delivery of safe blood.

Anti-inflammatory activity of roots of Cichorium intybus due to its inhibitory effect on various cytokines and antioxidant activity

Background: Cichorium intybus L. commonly known as chicory is one of the important medicinal plants commonly used in Ayurvedic system of medicine. It is commonly used for the treatment of diseases involving a khapa and pitta doshas. Traditionally, C. intybus is used for the treatment of inflammatory conditions, but there are only few in vitro studies reporting the anti-inflammatory activity of roots of chicory. Objective: Evaluation of anti-inflammatory activity of roots of chicory and mechanisms involved in it using in vivo models of inflammation. Materials and Methods: Albino Wistar rats of either sex weighing 150-200 g were used. Ethanolic and aqueous extracts of roots of chicory were prepared with the help of Soxhlet′s apparatus. The anti-inflammatory activity was studied using carrageenan-induced paw edema method and cotton pellet granuloma method. Levels of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-1 and activity of antioxidant enzymes such as catalase (CAT) and glutathione peroxidase (GPx) were estimated. Results: Chicory roots demonstrated significant dose-dependent decrease in paw edema in carrageenan-induced paw edema method. Chicory roots diminished the serum TNF-α, IL-6, and IL-1 levels. They also significantly attenuated the malonylaldehyde levels and increased the activities of CAT and GPx in paw tissue. Similarly, chicory roots demonstrated a significant decrease in granuloma formation in cotton pellet induced granuloma method. Conclusion: Chicory roots possess anti-inflammatory activity, and this might be due to the inhibition of various cytokines, antioxidant effects, and their free radical scavenging activity.

Primary squamous cell carcinoma of the parotid gland: a rare entity

Primary squamous cell carcinoma of the parotid gland is a rare aggressive malignancy. It is a rapidly advancing lesion which, if not recognised and treated early, results in high morbidity and mortality. Despite radical surgery and adjuvant radiotherapy, prognosis of this cancer continues to be poor. Careful clinical and histological examination is mandatory to differentiate this tumour from metastatic squamous cell carcinoma and other primary malignancies of the parotid. The authors hereby report the case of a 50-year-old male patient who presented with a progressively increasing, painless mass in parotid region of 6 months duration. An initial fine-needle aspiration cytology and subsequent histopathological examination confirmed that the tumour was squamous cell carcinoma. As no other primary source could be demonstrated in the patient, a final diagnosis of primary squamous cell carcinoma of parotid was offered. Currently the patient is on regular follow-up without any signs of recurrence.

Sister Mary Joseph's nodule: a rare cytologic presentation

Umbilical metastasis is one of the main characteristic signs of extensive neoplastic disease and is universally referred to as Sister Mary Josephs nodule. It indicates neoplasm of inner organs mostly located in the gastrointestinal tract or the pelvis. However, in approximately 15–30% the primary tumor remains occult. In most cases, Sister Mary Josephs nodule appears as an early and sometimes the only symptom of the malignancy. Here we report a rare fine needle aspiration (FNA) cytologic diagnosis of umbilical metastasis of an ovarian carcinoma.