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Synergism between the Two Membranes of the Blood-brain Barrier: Glucose and Amino Acid Transport
Get PDFBrain capillary endothelial cells, which are connected by extensive tight junctions and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains, form the blood-brain barrier (BBB). The polar distribution of transport proteins mediates glucose and amino acid (AA) homeostasis in the brain. The ability to isolate the luminal and abluminal membranes has permitted the study of each side of the BBB separately in vitro and yielded new information on BBB function. The two membranes have different characteristics. Facilitative transporters were found on both membranes in a position to permit the bidirectional transport of glucose, almost all amino acids and taurine. Na+-dependent transporters were only found on abluminal membranes. The Na+-dependent transporters on the abluminal side are capable of removing virtually all amino acids including acidic AA from the extracellular fluid of brain (ECF). The presence of Na+-dependent carriers on the abluminal membrane provides a mechanism by which the concentrations of AA, glucose and taurine in the ECF of brain may be maintained at optimal levels under physiological and pathophysiological circumstances. Facilitative carriers for glutamine (n) and glutamate (xg-) are found only in the luminal membrane of the BBB. This organization allows the net removal of acidic and nitrogen-rich AA from brain, and explains the low rate of glutamate and glutamine penetration into the central nervous system. The presence of a g-glutamyl cycle at the luminal membrane and Na+-dependent AA transporters at the abluminal membrane may serve to modulate movement of AA from blood to brain. The g-glutamyl cycle is expected to generate pyroglutamate within the endothelial cells. Pyroglutamate stimulates Na+-dependent AA transporters at the abluminal membrane thereby reducing net influx of AA the to brain. It is now clear the BBB may actively participate in the regulation of the AA content of the brain as well as contributing to the control of brain osmolarity
Consecutive Tumor Lysis Syndrome and Hepatic Failure after Transarterial Chemoembolization for Treatment of Hepatocellular Aarcinoma: A Case Report and Literature Review
Get PDFIntroduction: Acute tumor lysis syndrome (ATLS) and hepatic failure are fatal complications that can occur in patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE).Presentation of Case: We report the case of a 78-year-old man with HCC who had successive ATLS and hepatic failure after the first course of TACE. He succumbed due to rapid deterioration of his condition.Conclusion: We therefore concluded that awareness of the risks of ATLS and hepatic failure before administration of TACE is crucial in patients with HCC
Toxic Megacolon and Perforated Fungal Diverticulitis due to Mucor indicus Infection in a Patient with Chronic Myelogenous Leukemia
Get PDFIntroduction: Intestinal zygomycosis is a rare infection by the fungi zygomycetes that have little intrinsic pathogenicity in normal hosts and mainly affects immune compromised patients. Mucor indicus is a rare, emerging cause of intestinal zygomycosis with only 8 reported cases in English literature since 1986.Presentation of Case: We reported an unusual case of toxic megacolon, fungal diverticulitis with perforation and liver abscesses caused by Mucor indicus in a patient with chronic myelogenous leukemia (CML), B-lymphoid blast crisis and pancytopenia. The patient was treated with total colectomy and aggressive systemic anti-fungal regimens consisting of amphotericin, caspofungin and posaconazole. However, his fungal abscess in the liver persisted after colectomy, which was confirmed by liver biopsy at four months after total colectomy. His CML and B-lymphoid blast crisis was successfully treated with hyper-CVAD plus dasatinib and had been in complete remission. The patient was alive and continued to have stable fungal infection in the liver based on CT scan at 32 months after total colectomy, for which he has been on posaconazole monotherapy.Conclusions: Mucor indicus may cause a rare invasive zygomycosis that tends to involve gastrointestinal tract and to disseminate to the liver
Cold-active Moulds from Jammu and Kashmir, India as Potential Source of Cold-active Enzymes
Get PDFCold-active moulds have been isolated from the soil of ten selected sites of Jammu and Kashmir (India) in the winter season. Most of them turned out to be psychrotolerant except BPF-5 and BPF-6 which showed defective growth above 20oC, and thus were identified as psychrophilic moulds. BPF-5 was also found to form sexual structure at 4oC, while BPF-6 formed melanaceous filaments in old culture. The isolate BPF-5 has been identified as Truncatella angustata and BPF-6 as Psudogymnoascus sp. Among psychrotolerant moulds, the species of Cladosporium and Penicillium were found to be dominant taxa in terms of frequency and number of species while Rhizomucor sp., to be the most prolific mould under in vitro culture. Many of them formed adaptive structures and pigment. All of these isolates were able to utilize starch, cellulose, casein and tween-80 while many of them were able to use pectin and carboxy methyl cellulose (CMC) as sole carbon source at 4oC suggesting that they might be important sources of cold-adapted enzymes and other biomolecules. Although α-amylase from all the isolates showed residual cold-activity, that from BPF-6 exhibited the highest one suggesting it to be further explored for biotechnological applications
Differential Association between HER2/neu and Angiogenesis in Breast Cancer
Get PDFThe HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor and a member of the epidermal growth factor receptors (EGFR/ErbB) family. Over-expression of this oncogene is known to contribute to pathogenesis and aggressive progression in breast cancer. On the other hand, angiogenesis is a physiological process of forming new blood vessels from pre-existing ones; however it is essential for tumor growth and transitional from benign stage to malignant form and also fundamental process for metastasis of tumors. In this study the main aim was to investigate whether angiogenesis is the cause for increased aggressive behavior of HER2 overexpression subtype in breast cancer. A variety of approaches were employed to investigate the main aim: quantification of angiogenesis using a mouse cancer cells implanted model; Drabkin’s assay for hemoglobin measurement; morphology assessment of cell lines; Bio-Plex analysis of angiogenesis factors angiopoietin-2, follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-BB, PECAM-1 and VEGF; and reverse transcriptase-PCR on VEGFA and HIF-1 alpha genes expression. The data from this study showed that the AU-565 cell line which over-expresses HER2 receptors showed a significant decrease in both tumor weight and hemoglobin measurement when the cells were treated with anti-HER2 implanted in nude mice. Also, the data showed an increased expression of angiogenic factors and genes (mainly VEGF, VEGFA, Angiopoietin, and IL-8) in AU-565 as compared to MCF-7 cells, which have low expression of HER2 receptors. This suggests that breast cancer with HER2/neuoncogenes is associated with more angiogenic activities that result in an increased aggressive behavior of this form of cancer
Probiotic Dahi Containing Lactobacillus Acidophilus and Lactobacillus Plantarum Suppresses DMH Induced Preneoplastic lesions in early Colorectal Carcinogenesis in Wistar Rats
Get PDFThis study evaluated the chemopreventiveeffects of probiotic LaLpDahicontainingLactobacillus acidophilus LaVK2 and Lactobacillus plantarumLp9 alone or as an adjunct with piroxicam (PXC)in male Wistar rats administered 1,2-dimethylehydrazine dihydrochloride (DMH).Colorectal carcinogenesis was induced by injecting DMH subcutaneously (40mg/kg body weight) twice a week for 2 weeks. Rats were divided into five groups, twenty four in each group and fed with the buffalo milk or probiotic supplements (20g) in addition to basal diet for 32 weeks.The rats were fed with buffalo milk or probiotic Dahi alone or in combination with PXC in addition to basal diet ad libitumand euthanized at 8th, 16th and 32nd weeks of the experiment and examined for development of aberrant crypt foci (ACF), mucin-depleted foci (MDF) and proliferating cell nuclear antigen (PCNA) labeling index. Administration of DMH in rats induced formation of preneoplastic lesions (ACF and MDF) and increased PCNA index in colorectal tissue. Probiotic Dahi alone or in combination with piroxicam showed a significant (P0.05) protectiveeffects by loweringthe initiation and progression of DMH induced formation of preneoplastic lesions and PCNA labeling index.Theseobservations suggest that probiotic LaLp Dahi alone or in combination with PXC may be used as a potential nutraceutical intervention in prophylaxis and treatment of colorectal cancer
Imatinib and Thyroid Dysfunction in BCR-ABL Positive CML Patients
Get PDFBackground: Thyroid dysfunction is a known adverse effect of some tyrosine kinase inhibitors like sunitiniband sorafenib while imatinib hasbeen shown to induce hypothyroidism and increased requirement of levothyroxine in thyrectomizedpatients. Very few retrospective studies are available for CML patients treated with imatinib,which havedemonstrated conflicting effects on thyroid function.Experimental design: We have prospectively studied thyroid function at baseline and at 6 months of imatinib treatment in 30 newly diagnosed BCR-ABL positive CML patients.Results: Two (6.7%) patients had subclinical hypothyroidism at diagnosis with the prevalence not being different from general population. Though the TSH levels increased significantly from baseline (3.80±2.00 mIU/L vs. 3.14±1.65 mIU/L, p =0.016) after6 months of treatment, 90% of the patients remained euthyroid. Only 3 patients had subclinical hypothyroidism.Conclusion: Imatinib did not have any significant impact on thyroid function in CML patients but may possibly alter the peripheral metabolism of thyroid hormones
Short Interval Occurance of Papillary Thyroid Carcinoma Following Radiotherapy for Hodgkin’s Disease: a Case Report
Get PDFIntroduction: Hodgkin’s disease (HD) is a common pediatric malignancy that is treated with a combination of chemotherapy and radiation. Although cure rates are very high (~90%), secondary malignancies are not uncommon and radiation has been shown to be a risk factor for their development. Secondary malignant neoplasms (SMNs) of the thyroid gland are common solid tumors found in patients treated for HD. Current literature shows that these SMNs generally appear an average of 5-15 years later, even in patients under surveillance.Presentation of Case: We present 16 year old patient with secondary thyroid papillary carcinoma four years after completion of radiotherapy.Conclusion: This case may have implications for the future management and post radiation care of these patients
An Unusual Case of Presacral Carcinoid Tumor and the Approach of Management
Get PDFIntroduction: Gut derived neuroendocrine tumors (NETs) are a heterogenous group of tumors classified as Gastroenteropancreatic (GEP) NETs. These tumors can be found along the gastrointestinal tract from the foregut, mid, to the hindgut. They are referred to as carcinoid tumors due to their potential to secrete bioactive hormones.Presacral tumors are a subset of GEP NETs that are histologically similar. They are uncommon tumors that are found at the presacral space and are often clinically silent with no associated carcinoid syndrome. Presentation of Case: We report a case of 49 year old female who was diagnosed with a presacral carcinoid tumor. Her initial presentation, investigations that led up to the final diagnosis and management of the tumor are discussed. Conclusion: Presacral carcinoid tumors are NETs that are clinically and histologically similar to GEPs arising from the colon or rectum. Management of such tumors is often surgical resection of localized disease with a long follow-up of surveillance to detect recurrence and metastasis
A Case of Lung Cancer with Isolated Skip Metastasis to an External Iliac Lymph Node
Get PDFIntroduction: Isolated skip metastases to intra-abdominal lymph nodes from lung cancer are rare and management of such disease remains controversial. Presentation of case: We report a case of lung adenocarcinoma in the right upper lobe with isolated lymph node metastasis to an external iliac lymph node detected by Positron Emission Tomography (PET) scan which was confirmed histopathologically. Conclusion: Isolated intra-abdominal lymph nodes from lung cancer are a rare occurrence. In these patients, lymphadenectomy can be considered together with definitive treatment of the lung primary