Granulomatous and lymphocytic hypophysitis – are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities – granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T‐helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5–40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T‐cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.     

Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7,12-dimethylbenz[a]anthracene

Tangeretin, a citrus polymethoxyflavone, is an antioxidant modulator which has been shown to exhibit a surfeit of pharmacological properties. The present study was hypothesized to explore the therapeutic activity of tangeretin against 7,12-dimethylbenz[a]anthracene (DMBA) induced kidney injury in mammary tumor bearing rats. Recently, we have reported the chemotherapeutic effect of tangeretin in the breast tissue of DMBA induced rats. Breast cancer was induced by “air pouch technique” with a single dose of 25 mg/kg of DMBA. Tangeretin (50 mg/kg/day) was administered orally for four weeks. The renoprotective nature of tangeretin was assessed by analyzing the markers of oxidative stress, proinflammatory cytokines and antioxidant competence in DMBA induced rats. Tangeretin treatment revealed a significant decline in the levels of lipid peroxides, inflammatory cytokines and markers of DNA damage, and a significant improvement in the levels of enzymatic and non-enzymatic antioxidants in the kidney tissue. Similarly, mRNA, protein and immunohistochemical analysis substantiated that tangeretin treatment notably normalizes the renal expression of Nrf2/Keap1, its downstream regulatory proteins and the inflammatory cytokines in the DMBA induced rats. Histological and ultrastructural observations also evidenced that the treatment with tangeretin effectively protects the kidney from DMBA-mediated oxidative damage, hence, proving its nephroprotective nature.     

Neurochemical changes related to ageing in the rat brain and the effect of DL-alpha-lipoic acid

Age-related impairments of cognitive and motor function have been linked to a number of deleterious morphological and functional changes involving different areas of the brain. Loss of neurotransmitters, their receptors and responsiveness to neurotransmitters are key manifestations of neurological ageing and age-related disorders. In the present investigation we have evaluated the effect of DL-alpha-lipoic acid on neurotransmitters in discrete brain regions of young and aged rats. The levels of neurotransmitters were found to be lowered in aged rats. Moreover, DL-alpha-lipoic acid treated aged rats showed a increase in the status of dopamine, serotonin and norepinephrine. The results of this study provide evidence that DL-alpha-lipoic acid (a potent antioxidant) treatment can improve neurotransmitters during ageing. Hence, it can be concluded that DL-alpha-lipoic acid act as a potent neuromodulator in the brain of aged rats.     

Effects of aqueous extracts of garlic (Allium sativum) and neem (Azadirachta indica) leaf on hepatic and blood oxidant-antioxidant status during experimental gastric carcinogenesis

The modifying effects of aqueous extracts of garlic and neem leaf during the pre-initiation and post-initiation phases of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in male Wistar rats. The extent of lipid peroxidation and the status of phase II biotransformation enzymes such as glutathione peroxidase and glutathione-S-transferase that use reduced glutathione (GSH) as substrate were used to biomonitor the chemopreventive potential of these extracts. Enhanced lipid peroxidation in the liver and blood of tumor-bearing animals was accompanied by significant decreases in the activities of GSH-dependent antioxidants in the pre-initiation as well as in the post-initiation phases. Our results suggest that the modulatory effects of garlic and neem leaf on hepatic and blood oxidant-antioxidant status may play a key role in preventing cancer development at extrahepatic sites.     

Effect of DL-alpha-lipoic acid on neural antioxidants in aged rats.

The effect of DL-alpha-lipoic acid on lipid peroxidation and antioxidants were evaluated in various brain regions of young and aged rats. In aged rats, the levels of ascorbic acid, alpha-tocopherol and glutathione were low whereas the lipid peroxidation rate, as revealed by malonaldehyde content, was found to be high. Lipoic acid, an antioxidant, was administered intraperitoneally (100 mg/kg body weight/day) for 7 and 14 days. Lipoate-administered aged rats brought about reduction in lipid peroxidation and elevation in the levels of antioxidants. The modulatory effect of lipoate in decreasing age-associated alterations observed in our study proves its role as a potent antioxidant in the brain of aged rats.     

Tension pneumoventricle following exposure of shunt chamber

Pneumocephalus is the presence of air within the intracranial vault. Intraventricular pneumocephalus, also known as pneumoventricle is relatively rare and commonly occurs following cerebrospinal fluid diversion procedures. This may occur immediately or be delayed. Although a small amount of pneumoventriculus is asymptomatic and may not require any treatment, when present under tension it needs to be evacuated. We present a case of tension pneumoventricle following exposure of the shunt chamber, which resulted in deterioration of the patients' neurological condition and required evacuation.     

Progenitor migration to the thymus and T cell lineage commitment

T cells developing in the thymus are ultimately derived from bone marrow (BM) hematopoietic stem cells (HSCs). An understanding of the developmental steps between HSCs and T cells is important for gaining insight into cancers of the T lineage, improving T cell reconstitution after BM transplantation, and also to help ameliorate immunological defects in aging. In this article, we summarize our current understanding of the inter-related fields of early T cell development and thymic aging, and briefly discuss major unresolved questions in this field.     

Immunomodulatory effect of DL-α-lipoic acid in aged rats

Senescence is the result of an imbalance between free radical production and antioxidant defenses, with concomitant oxidative stress and age-dependent functional decline. This process is especially evident in the immune cells, which use free radicals in their functions and suffer a senescent deterioration probably linked to oxygen stress. We hypothesize that oxidative damage and antioxidant imbalance may play a critical role in the immune dysfunction in aging. In the present study, we investigated this hypothesis in aged rats by treatment with alpha-lipoic acid (α-LA). We studied the effect of α-LA on immune function by examining immunomodulating factors in the plasma. Then we examined oxidative damage and antioxidant defense systems in the plasma. We found out that immune dysfunction in aged animals is associated with increased oxidative damage and decreased antioxidant status and treatment with α-LA effectively elevated immune function, decreased oxidative insult and enhanced antioxidant status. These results suggest that α-LA may be effective in improving immune function in aging through decreasing oxidative damage and revitalizing antioxidants in blood.