Arabinose confers protection against intestinal injury by improving integrity of intestinal mucosal barrier.

There is a growing amount of research that highlights the significant involvement of metabolic imbalance and the inflammatory response in the advancement of colitis. Arabinose is a naturally occurring bioactive monosaccharide that plays a crucial role in the metabolic processes and synthesis of many compounds in living organisms. However, the more detailed molecular mechanism by which the administration of arabinose alleviates the progression of colitis and its associated carcinogenesis is still not fully understood. In the present study, arabinose is recognized as a significant and inherent protector of the intestinal mucosal barrier through its role in preserving the integrity of tight junctions within the intestines. Also, it is important to note that there is a positive correlation between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), as well as chemically-induced colitis in mice, and lower levels of arabinose in the bloodstream. In two mouse models of colitis, caused by dextran sodium sulfate (DSS) or by spontaneous colitis in IL-10-/- mice, damage to the intestinal mucosa was reduced by giving the mice arabinose. When arabinose is administrated to model with colitis, it sets off a chain of events that help keep the lysosomes together and stop cathepsin B from being released. During the progression of intestinal epithelial injury, this process blocks myosin light chain kinase (MLCK) from damaging tight junctions and causing mitochondrial dysfunction. In summary, the results of the study have provided evidence supporting the beneficial effects of arabinose in mitigating the progression of colitis. This is achieved through its ability to avoid dysregulation of the intestinal barrier. Consequently, arabinose may hold promise as a therapeutic supplementation for the management of colitis.

Astrocyte-neuron lactate transport in the ACC contributes to the occurrence of long-lasting inflammatory pain in male mice.

Lactate transport is an important means of communication between astrocytes and neurons and is implicated in a variety of neurobiological processes. However, the connection between astrocyte-neuron lactate transport and nociceptive modulation has not been well established. Here, we found that Complete Freund's adjuvant (CFA)-induced inflammation pain leads to a significant increase in extracellular lactate levels in the anterior cingulate cortex (ACC). Inhibition of glycogenolysis and lactate release in the ACC disrupted the persistent, but not acute, inflammation pain induced by CFA, and this effect was reversed by exogenous L-lactate administration. Knocking down the expression of lactate transporters (MCT1, MCT4, or MCT2) also disrupted the long lasting inflammation pain induced by CFA. Moreover, glycogenolysis in the ACC is critical for the induction of molecular changes related to neuronal plasticity, including the induction of phospho- (p-) ERK, p-CREB, and Fos. Taken together, our findings indicate that astrocyte-neuron lactate transport in the ACC is critical for the occurrence of persistent inflammation pain, suggesting a novel mechanism underlying chronic pain.

[Effect of L-arabinose on glucose and lipid metabolism in type 2 diabetic rats].

OBJECTIVE: To investigate the effect of L-arabinose on glucose and Organ and islet in type 2 diabetic rats. METHODS: Male Wistar rats were fed high-sugar and high-fat diet after 8 weeks, then inject streptozotocin intraperitoneally according to 25 mg/kgbw dose to establish animal models of type 2 diabetes, and fed L-arabinose according to a low dose (50 mg/kgbw ), medium dose (150 mg/kgbw) and high dose (500 mg/kgbw) ,the animal be fed acarbose (20 mg/kgbw) as a positive control, the use of L-arabinose and acarbose were prepared in the dextrin (0.36 g/ml) and sucrose (0.04 g/ml) of the suspension, free to eat water. OGTT after 4 weeks, After animal death, rat liver, epididymal fat and cecum were weighed and calculate the ratio of organ weight. Results compared with model group, low, animals with L-arabinose-intervention those blood glucose response had a significant impact, 30 min, 60 min, 120 min blood glucose values and AUC were significantly lower than the model group (P < 0.05), of which medium dose is most significant (P < 0.01). L-arabinose intervention increased cecal weight and showed protective effect on beta-cell. CONCLUSION: L-arabinose long-term intervention can improve glucose tolerance in type 2 diabetic rats, this effect may be related to L-arabinose inhibition of digestive enzymes and the protective effect on beta-cell.

Primary T-cell lymphoma of the brain in children: a case report and literature review.

Described here are the clinical features and results of treatment in a 10-year-old Saudi Arabian girl with primary T-cell lymphoma of the central nervous system. At presentation the patient had nystagmus and ataxia. The diagnosis was established by tissue biopsy obtained from the cerebellum. Therapy included cranio-spinal irradiation and combination chemotherapy of a systemic high dose of methotrexate, cytosine, arabinoside, and L-asparaginase. Remission was obtained easily but was interrupted by a local intracranial relapse 57 months after diagnosis (37 months after cessation of therapy; at present the patient is still alive and receiving palliative treatment). This report is warranted because of the rarity of this condition in children.

Rational design of arabinosyl nucleosides as antitumor and antiviral agents.

The rational design of antitumor and antiviral agents must ultimately take advantage of biochemical differences between normal host cells and transformed cells. The initial experiments must be performed with subcellular or cellular model systems. For the studies with arabinosyl nucleosides we have chosen those enzyme systems, synthesizing DNA and RNA; being precursor analogues, the different arabinosyl nucleosides have been added in the triphosphate state to the different DNA- and RNA polymerase assays. 1-beta-D-Arabinofuranosylcytosine-5'-triphosphate has been found to inhibit the RNA-dependent DNA polymerases (isolated from oncogenic RNA viruses) 200-fold more sensitively than viral and cellular DNA-dependent DNA polymerases. Recent results, showing that RNA-leukemia-virus-related sequences are present in DNA of some human leukemia patients might support the assumption that the efficacy of this antimetabolite in the treatment of acute leukemia is due to its, at least relative selective inhibitory activity on reverse transcriptase. 9-beta-D-Arabinofuranosyladenine-5'-triphosphate is a strong inhibitor of cellular DNA polymerases with the cytological consequence of an inhibition of cell proliferation. The clinical benefit of the compound in treatment of tumors is dependent on their levels of adenosine deaminase. The triphosphate of this compound is a 100-fold more sensitive inhibitor of the herpesvirus DNA polymerase compared to the cellular replicative DNA polymerase. In addition the analogue, incorporated into herpesvirus DNA, acts as chain terminator. These effects are the biochemical basis for the highly selective antiherpesvirus activity of this antimetabolite. The anomer 9-alpha-D-arabinofuranosyladenine-5'-triphosphate only inhibits cellular replicative DNA polymerase and has no effect on herpesvirus DNA polymerase. Consequently this agent acts only cytostatically and not antivirally. Concerning 1-beta-D-arabinofuranosyluracil and 1-beta-D-arabinofuranosylthymine no pronounced antitumor or antiviral effect is known.

Selective tumor DNA synthesis inhibition: in vivo prodrug activation by an exogenous enzyme.

Using the combination of alpha-L-arabinofuranosidase from Aspergillus niger with beta-peltatin A-alpha-L-arabinofuranoside, the selective effect of a new cancer of chemotherapy method based on a pH-dependent activation of cancerostatic prodrugs by exogenous enzymes was studied. In comparative experiments the selectivity of prodrug activation was measured by 3H-thymidine incorporation in tumor and normal tissues of CBA mice inoculated im with the transplantable mammary carcinoma, MA-21224. The results show that this special type of carrier principle may lead to a higher degree of selectivity than the usual direct application of cancerostatic drugs.

Effect of 9-beta-D-arabinofuranosyladenine 5'-monophosphate and 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate on experimental herpes simplex keratitis.

Treatment of established experimental keratitis caused by herpes simplex virus with 9-beta-d-arabinofuranosyladenine 5'-monophosphate (Ara-AMP) or 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (Ara-HxMP) showed that the Ara-AMP, in a concentration of 2 or 20%, had a significant effect on the keratitis but that 0.4% Ara-HxMP showed only minimal activity. Ara-AMP was also effective in the treatment of idoxuridine-resistant keratitis. No local toxicity with a high concentration (20%) of Ara-AMP was seen, but the duration of therapy was brief.

Inhibition of experimental deoxyribonucleic acid virus-induced encephalitis by 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate.

9-beta-d-Arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly controlled the development of encephalitis produced by deoxyribonucleic acid viruses in mice. In most experiments the activities of ara-HxMP and 9-beta-d-arabinofuranosyladenine (ara-A) were determined simultaneously. In the intracerebral (target organ) and intravenous therapy experiments, ara-HxMP had a pronounced advantage over ara-A since the water solubility of ara-HxMP enabled it to be used in much higher concentrations. In experiments where the two drugs were administered intraperitoneally or orally they exhibited similar activity. In several intraperitoneal therapy experiments ara-HxMP was tested alone, using various treatment schedules and dosages. In these experiments, efficacy was observed in groups that had treatments initiated as late as 72 h after virus inoculation.

Efficacy of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate in therapy of equine abortion virus-induced hepatitis in hamsters.

Equine abortion virus (EAV)-induced hepatitis in hamsters presents an interesting animal model for the evaluation of drugs possessing anti-deoxyribonucleic acid virus activity. These experiments demonstrate that 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP), a new synthetic, water-soluble, antiviral agent, effectively controls this disease in hamsters with a therapeutic index of approximately 60. Ara-HxMP prevented hepatitis-associated deaths in hamsters, reduced the titer of EAV developing in hamsters, and inhibited the increase of serum glutamic pyruvic transaminase in EAV-infected hamsters.

Viral keratitis-inhibitory effect of 9-beta-D-arabinofuranosylhypoxanthine 5'-monophosphate.

Topical application of 9-beta-d-arabinofuranosylhypoxanthine 5'-monophosphate (ara-HxMP) significantly inhibited the development of keratitis induced by types 1 and 2 herpes simplex virus and vaccinia virus in the eyes of rabbits. Parameters for evaluation of efficacy were infectivity (corneal opacity, lesion size, and type), Draize (erythema, conjunctival swelling, and discharge), and reduction in titer of recoverable virus from the eye. When the relative efficacy of the related compounds 9-beta-d-arabinofuranosyladenine (ara-A), ara-A 5'-monophosphate (ara-AMP), and ara-Hx was determined against type 1 herpes simplex virus in a parallel experiment, the more water-soluble compounds (ara-HxMP, ara-AMP) were the most effective. The relative efficacy of ara-A was also determined against type 2 herpes and vaccinia virus-induced keratitis. Mortality in rabbits due to central nervous system involvement caused by types 1 and 2 herpes simplex virus was inhibited. Ara-HxMP was not discernibly toxic to the eye at concentrations of at least 20%; efficacy was still discernible with a 0.1% solution.

Evaluation of four antiviral agents in the treatment of herpes simplex encephalitis in a rat model.

Three hundred four animals were used for the systematic evaluation of the in vivo efficacy of 5-iodo-2'-deoxyuridine (IUDR), cytosire arabinoside, 9-beta-arabinofuranosyladenine, and isoprinosine in the therapy of herpes simplex encephalitis in an adult rat model. Type 1 herpes simplex virus was inoculated intracerabrally, and drug was administered by the intraperitoneal route. All experiments included tests for toxicity and viral controls, Eight sets of experiments were used for evaluation of ttherapy with IUDR; the inoculum ranged from 64 to 2,000 TCID50, dose of drug from 0.1 mg/g to 1.0 mg/g per day, and duration of therapy from one to five days. There was no significant improvement in the number of animals surviving or in the survival time when the viral controls were compared with mice in treated groups. A slight trend toward increased survival time and decreased titer of virus in the brains of animals treated with IUDR was noted in the group that received the largest dose. Three or four sets of experiments were used to evaluate each of the other three antiviral drugs. Results were similar to those reported for IUDR. These results indicate a need for further studies, including investigations of the pharmacology and toxicity of these antiviral agents, to establish more clearly the dosages of drug that are therapeutic, those that are toxic, and ratios of these dosages.

Treatment of variola major with adenine arabinoside.

A double-blind study of the efficacy of adenine arabinoside in the treatment of patients with variola major was conducted. Adenine arabinoside (20 mg/kg of body weight) was given to patients intravenously every 24 hr for seven days in a 8-hr infusion. Five of the nine patients receiving adinine arabinoside died, and four of 11 patients receiving placebo died. Mortality was related to the severity of illness for both groups of patients. No difference was found between the drug and control groups in number of febrile days after initiation of therapy or in the period during which it was possible to isolate virus from skin lisions, throat swabs, and sources of clotted blood. Formation of scabs on skin lesions was complete 8.3 days after the initiation of therapy for the drug group and after 11.3 days for the control group. The findings suggest that adenine arabinoside is not effective in the chemotherapy of smallpox.

Herpes simplex virus skin infection in hairless mice: treatment with antiviral compounds.

A hairless mouse-herpes simplex virus skin infection experimental model was used to evaluate the efficacy of the antiviral compounds 9-beta-d-arabinofuranosyladenine (ara-A), 5-iodo-2'-deoxyuridine (IUdR), and 6-azauridine (aza-U). Ara-A and IUdR, when administered intraperitoneally by several different dosage schedules, reduced the severity of cutaneous herpetic lesions and the incidence of paralysis and increased significantly the number of survivors. A more rapid healing of the lesions and an increase in the mean survival time also was observed. A delay of 24 to 48 h in the initiation of treatment after the infection was more effective than treatments started at the time of inoculation. Treatment with ara-A was somewhat superior to that with IUdR, but aza-U was totally ineffective. Enhancement of the evolution of the infection was noted after treatment with aza-U.