Efficiency of Resistant Starch and Dextrins as Prebiotics: A Review of the Existing Evidence and Clinical Trials.

In well-developed countries, people have started to pay additional attention to preserving healthy dietary habits, as it has become common knowledge that neglecting them may easily lead to severe health impairments, namely obesity, malnutrition, several cardiovascular diseases, type-2 diabetes, cancers, hypertensions, and inflammations. Various types of functional foods were developed that are enriched with vitamins, probiotics, prebiotics, and dietary fibers in order to develop a healthy balanced diet and to improve the general health of consumers. Numerous kinds of fiber are easily found in nature, but they often have a noticeable undesired impact on the sensory features of foods or on the digestive system. This led to development of modified dietary fibers, which have little to no impact on taste of foods they are added to. At the same time, they possess all the benefits similar to those of prebiotics, such as regulating gastrointestinal microbiota composition, increasing satiety, and improving the metabolic parameters of a human. In the following review, the evidence supporting prebiotic properties of modified starches, particularly resistant starches and their derivatives, resistant dextrins, was assessed and deliberated, which allowed drawing an interesting conclusion on the subject.

Carbohydrate hastens hypervolemia achieved through ingestion of aqueous sodium solution in resting euhydrated humans.

PURPOSE: Ingesting beverages containing a high concentration of sodium under euhydrated conditions induces hypervolemia. Because carbohydrate can enhance interstitial fluid absorption via the sodium-glucose cotransporter and insulin-dependent renal sodium reabsorption, adding carbohydrate to high-sodium beverages may augment the hypervolemic response. METHODS: To test this hypothesis, we had nine healthy young males ingest 1087 ± 82 mL (16-17 mL per kg body weight) of water or aqueous solution containing 0.7% NaCl, 0.7% NaCl + 6% dextrin, 0.9% NaCl, or 0.9% NaCl + 6% dextrin under euhydrated conditions. Each drink was divided into six equal volumes and ingested at 10-min intervals. During each trial, participants remained resting for 150 min. Measurements were made at baseline and every 30 min thereafter. RESULTS: Plasma osmolality decreased with water ingestion (P ≤ 0.023), which increased urine volume such that there was no elevation in plasma volume from baseline (P ≥ 0.059). The reduction in plasma osmolality did not occur with ingestion of solution containing 0.7% or 0.9% NaCl (P ≥ 0.051). Consequently, urine volume was 176-288 mL smaller than after water ingestion and resulted in plasma volume expansion at 60 min and later times (P ≤ 0.042). In addition, net fluid balance was 211-329 mL greater than after water ingestion (P ≤ 0.028). Adding 6% dextrin to 0.7% or 0.9% NaCl solution resulted in plasma volume expansion within as little as 30 min (P ≤ 0.026), though the magnitudes of the increases in plasma volume were unaffected (P ≥ 0.148). CONCLUSION: Dextrin mediates an earlier hypervolemic response associated with ingestion of high-sodium solution in resting euhydrated young men. (247/250 words).

Effectiveness of barrier agents for preventing postoperative bowel obstruction after laparoscopic surgery: a retrospective cohort study.

PURPOSE: The effectiveness of using anti-adhesion agents in laparoscopic surgery is controversial. We compared the outcomes of patients exposed to anti-adhesion agents (barrier group) with those of patients not exposed (no barrier group) in laparoscopic surgery. METHODS: Using a nationwide claim-based database in Japan, we analyzed data from patients who underwent laparoscopic surgery between 2005 and 2019 and compared the patient characteristics and the proportion of those with bowel obstruction between the barrier and no barrier groups. We also performed several sensitivity and subgroup analyses. RESULTS: Of the 57,499 patients who met the inclusion criteria, 14,360 and 43,139 were assigned to the barrier and no barrier groups, respectively. The proportion of patients with a bowel obstruction in the two groups did not differ among all patients hospitalized for obstruction (1.1 vs. 1.1%, p = 0.63) and those requiring surgery (0.2 vs. 0.2%, p = 0.39). In the sensitivity analysis with propensity score matching, the incidences of bowel obstruction between the barrier and non-barrier groups were equivocal (1.3 vs. 1.6%), but statistically marginal (chi-square test, p = 0.035; log-rank test, p = 0.09). CONCLUSION: The use of barrier agents for adhesive prevention did not show clear effectiveness for the prevention of bowel obstruction after laparoscopic surgery for unselected cases. Further studies focusing on more specific procedures are needed.

The longevity of Aedes aegypti mosquitoes is determined by carbohydrate intake / [A longevidade de mosquitos Aedes aegypti é determinada pela ingestão de carboidrato]

Aedes aegypti is the vector of several viral diseases. The main way to control these diseases is to fight the vector. Thus, it is necessary to breed mosquitoes in the laboratory in order to develop strategies to control these insects. In laboratories, different carbohydrates are used for feeding mosquitoes. The aim of this study is to evaluate the longevity and the weight of Ae. aegypti fed with different carbohydrates diets. As methods, 120 mosquitoes were distributed in insectaries and each group received a different diet, based on honey, dextrose or maltodextrin. To assess the longevity, survival analysis was performed using the Long Rank test and chi square test. To assess the weight, the dead insects were frozen and weighed at the end of the experiment. As results it was observed that mosquitoes fed with the honey, maltodextrin and dextrose diet lived on average 33, 35 and 47 days respectively. When weight was assessed, mosquitoes fed with honey weighed 125 ± (35.3) µg, while those fed with dextrose and maltodextrin weighed 225 ± (35.3) µg and 275 ± (35.3) µg respectively. The results show that the intake of dextrose and maltodextrin by Ae. aegypti adults increases their survival and their weight.(AU)

O Aedes aegypti é vetor de várias doenças virais. A principal maneira de controlar essas doenças é combatendo o seu vetor. Nesse sentido, é necessário criar esses mosquitos em laboratório, visando desenvolver estratégias de controle. Nos laboratórios, diferentes carboidratos são utilizados na alimentação de mosquitos. O objetivo deste estudo é avaliar longevidade e peso de Ae. aegypti alimentados com diferentes fontes de carboidratos. Como método, distribuíram-se 120 mosquitos insetários. Cada grupo recebeu uma dieta diferente à base de mel, dextrose ou maltodextrina. Para avaliar a longevidade, a análise de sobrevida foi realizada pelo teste de Logrank e pelo teste de qui quadrado. Para avaliar o peso, os insetos mortos foram congelados e pesados ​​no final do experimento. Como resultado, observou-se que os mosquitos alimentados com a dieta à base de mel, maltodextrina e dextrose viveram em média 33, 35 e 47 dias, respectivamente. Com relação ao peso, os mosquitos alimentados com mel pesavam 125 ± (35,3)µg, enquanto os alimentados com dextrose e maltodextrina pesavam 225 ± (35,3)µg e 275 ± (35,3)µg, respectivamente. Os resultados mostram que a ingestão de dieta à base de dextrose e maltodextrina por Ae. aegypti adultos aumenta sua sobrevivência e seu peso.(AU)

Evaluation of adhesion barrier types in a rat hepatectomy-induced adhesion model.

BACKGROUND: Adhesion formation after hepatectomy creates problems for repeat hepatectomy. This study aimed to compare the effectiveness of a spray (AdSpray) and sheet adhesion barrier (Seprafilm) in a rat hepatectomy-induced adhesion model. METHODS: Thirty male Sprague-Dawley rats underwent partial resection of the left lateral liver lobe. They were randomly assigned to control (n = 10), AdSpray (n = 10), and Seprafilm groups. Seven days after surgery, the animals were sacrificed, and adhesions at the hepatic resection surface were blindly evaluated. RESULTS: In the control group, adhesions were formed in all 10 animals (100%), with a 69% adhesion extent (mean). In the AdSpray group, the incidence of adhesions (40%) and the adhesion extent (mean, 10%) were significantly lower than in the control group (incidence; p = 0.0147, adhesion extent; p = 0.0007). In the Seprafilm group, the incidence of adhesions was 70%. The adhesion extent of Seprafilm (mean, 30%) was significantly lower than in the control group (p = 0.0492). No significant differences were observed between the AdSpray and Seprafilm groups. As for histopathological examination, animals in the AdSpray group showed a similar healing profile to that of the control group without delayed healing and regeneration of mesothelial cells. In contrast, the Seprafilm group showed ongoing foreign body reaction to Seprafilm, and regeneration of mesothelial cells was immature at 7 days. CONCLUSIONS: Both the spray-type gel and sheet adhesion barriers significantly reduced adhesion formation after hepatectomy. The spray-type adhesion barrier caused no adverse events and induced favorable healing. These adhesion barriers may be effective in hepatectomy. Further animal studies and clinical trials are required to determine their benefits in clinical use.

Bioreduction-ruptured nanogel for switch on/off release of Bcl2 siRNA in breast tumor therapy.

In present study, gene concentrated as well as bioreduction-ruptured nanogel with local enrichment positive charge while low cytotoxicity was developed for Bcl2 siRNA delivery featured in intracellular switch on/off controlled release. Dynamic covalent bond crosslinked nanogel was formed by thiolated PEI of 1.8 kDa(PEI-1.8 kDa)and biodegradable dextrin. Once nanogel was uptake by tumor cells, high concentration of glutathione (GSH) in cytosol could bioreducible -degrade and rupture the crosslink of this dextrin nanogel (DSP) into hypotoxic PEI-1.8 kDa and dextrin, following by burst release of packed siRNA and minimizing the restriction of polymer material for siRNA transcription. This switch on/off siRNA release strategy for gene therapy exhibited equal level of the deregulation of Bcl2 protein expression determined by western blot analysis compared with cationic PEI with 25 kDa molecular weight (PEI-25 kDa) in vitro. Moreover, the gene concentrated DSP based on hypotoxic PEI-1.8 kDa and biodegradable dextrin could be administrated intravenously for systematic therapy on safely. Tumor suppression study of DSP also exhibited a superior antitumor activity in 4T1-luc tumor cell bearing BALB/C mice. Furthermore, it exhibited lower cytotoxicity, almost none hemotoxicity, moreover avoiding recognition and clearance by RES system in healthy mice. Overall, these findings suggest that this reduction-sensitive while bioreduction-ruptured polymer nanogel is an innovative strategy and holds great promise for gene and drug delivery.

The effect of soluble fiber dextrin on postprandial appetite and subsequent food intake in healthy adults.

OBJECTIVES: This crossover study investigated the effect of consuming a beverage that contains soluble fiber dextrin (SFD) on appetite and food intake in adults to test the hypothesis that beverages that contain 10 or 20 g of fiber from SFD would be more satiating than the control beverage. METHODS: Forty-one participants consumed lunch with a beverage that contained 0 g, 10 g, or 20 g of fiber from SFD. Appetite questionnaires were completed and blood samples collected immediately before lunch and at regular intervals over the following 150 min. Then, participants were provided with an afternoon snack and the amount eaten was recorded. Participants then left the laboratory but were asked to complete hourly appetite questionnaires and record food intake for the remainder of the day. RESULTS: Consuming SFD had no effect on appetite over the 150 min after consumption of the lunch meal (P > 0.05). Hunger and desire to eat were lower and fullness higher after consumption of the beverage that contained 20 g of fiber from SFD (P < 0.05) after participants left the laboratory. There was no effect of consuming SFD on food intake at the snack meal or for the rest of the day (P > 0.05). Plasma glucose-dependent insulintropic polypeptide was lower during the 150 min after consumption of 20 g fiber from the SFD beverage (P < 0.05). There was no treatment effect on the plasma concentration of other biomarkers of glycemic response or appetite (P > 0.05). CONCLUSIONS: Overall, the study results did not show an effect of SFD on appetite, food intake, and plasma markers of appetite for the first 150 min postconsumption. Further research is required to quantify how SFD influences appetite several hours after consumption.

Evaluation of a Spray-type, Novel Dextrin Hydrogel Adhesion Barrier Under Laparoscopic Conditions in a Porcine Uterine Horn Adhesion Model.

STUDY OBJECTIVE: To establish a porcine uterine horn adhesion model that mimicked laparoscopic procedures and use it to investigate the effect of a spray-type, novel dextrin hydrogel adhesion barrier (AdSpray; Terumo Corporation, Tokyo, Japan) on postsurgical adhesions. DESIGN: A single-blind randomized controlled trial (Canadian Task Force Classification I). SETTING: A Certified animal research facility. SUBJECTS: Sixteen female pigs. INTERVENTIONS: All animals underwent laparoscopically assisted adhesion-inducing surgery. The uterine horns and the peritoneum of the pelvic sidewall were injured. In the experimental group, AdSpray was applied to the injured site, and the handling of the sprayer was assessed. At 28 ± 1 days after surgery, animals were sacrificed, and adhesions at the injured site were evaluated. Uterine horn suture sites were examined under a light microscope to assess healing of the incised wound, the inflammatory reaction, abscess, and the foreign body reaction to the surgical suture. MEASUREMENTS AND MAIN RESULTS: The control group showed severe adhesions over the entire surface interface at the uterine horn suture sites and peritoneal resection site. Compared with the control treatment, AdSpray exhibited a higher percentage of adhesion-free sites (p < .001) and reduced the total adhesion score (p < .001). In the AdSpray group, no inflammation or abscess formation was observed on histopathological examination, and ideal healing of the suture sites was confirmed in all cases. CONCLUSION: Based on the results of the present study, the novel dextrin hydrogel shows excellent adhesion prevention and can be easily applied during laparoscopy using a dedicated sprayer.

HPMA copolymer-phospholipase C and dextrin-phospholipase A2 as model triggers for polymer enzyme liposome therapy (PELT).

'Polymer Enzyme Liposome Therapy' (PELT) is a two-step anticancer approach in which a liposomal drug and polymer-phospholipase conjugate are administered sequentially to target the tumour interstitium by the enhanced permeability and retention effect, and trigger rapid, local, drug release. To date, however, the concept has only been described theoretically. We synthesised two polymer conjugates of phospholipase C (PLC) and A2 (PLA2) and evaluated their ability to trigger anthracycline release from the clinically used liposomes, Caelyx® and DaunoXome®. N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-PLC and a dextrin-PLA2 were synthesised and their enzymatic activity characterised. Doxorubicin release from polyethyleneglycol-coated (PEGylated) Caelyx® was relatively slow (<20%, 60 min), whereas daunomycin was rapidly released from non-PEGylated DaunoXome® (∼87%) by both enzymes. Incubation with dextrin-PLA2 triggered significantly less daunomycin release than HPMA copolymer-PLC, but when dextrin-PLA2 was pre-incubated with α-amylase, the rate of daunomycin release increased. DaunoXome®'s diameter increased in the presence of PLA2, while Caelyx®'s diameter was unaffected by free or conjugated PLA2. Dextrin-PLA2 potentiated the cytotoxicity of DaunoXome® to MCF-7 cells to a greater extent than free PLA2, while combining dextrin-PLA2 with Caelyx® resulted in antagonism, even in the presence of α-amylase, presumably due to steric hindrance by PEG. Our findings suggest that in vivo studies to evaluate PELT combinations should be further evaluated.

Novel pH-responsive dextrin nanogels for doxorubicin delivery to cancer cells with reduced cytotoxicity to cardiomyocytes and stem cells.

The aim of this study was to develop pH-responsive dextrin nanogels (DNGs) capable of triggered intracellular DOX release at the lower pH of cancer cells. DNGs were prepared by an emulsion cross-linking method using glyoxal as cross-linker to create an acid-labile bond. A higher molecular weight of dextrin with increasing mole ratio of dextrin to glyoxal decreased the average diameter of DNGs. DNGs showed slightly negative surface charge and pH-responsive behavior. The in vitro drug release was slow at pH 7.4 and increased with decreasing pH (pH 5>6.8). The cytotoxicity of DOX-loaded DNGs in mesenchymal stem cells and cardiomyocytes was lower than that of free DOX. Moreover, DOX-loaded DNGs were efficiently internalized by tumor cells with rapid release of DOX into the nucleus. Thus, DOX-loaded DNGs were successful for intracellular targeted anti-tumor drug delivery and reducing side-effects to non-tumor cells such as cardiomyocytes and stem cells.

Safety profile of dextran-spermine gene delivery vector in mouse lungs.

A nano-sized polymer, dextran-spermine (D-SPM), was shown to have the capacity to deliver gene to the lung of mouse via intranasal route. In this study, assessments on the safety profile of D-SPM were performed to complement the gene expression results. African green monkey kidney fibroblast (COS-7) and human adenocarcinoma breast (MCF-7) cells transfected with D-SPM/pDNA showed massive reduction in the number of viable cells. As for in vivo study, elevated level of neutrophils was observed, despite the minimal level of pro-inflammatory cytokines (TNF-alpha, IL-12, IFN-gamma) detected in the bronchoalveolar lavage fluid (BALF) of mice treated with the D-SPM/pDNA complexes. Histology profile examinations of the lungs showed mild inflammatory responses, with inflamed areas overlap with healthy areas. Although reduction of mice weight was seen at day 1 post administration, the mice did not show any sign of abnormal behavior or physical appearance. Biodistribution study was performed to determine the ability of the D-SPM/pDNA complexes to infiltrate to other non-intended organs. The result showed that the D-SPM/pDNA complexes were only localized at the lung and no gene expression was detected in other organs or blood. In short, these results indicate that the D-SPM/pDNA exhibited mild toxicity in the mouse lungs.

Differential responses of the incretin hormones GIP and GLP-1 to increasing doses of dietary carbohydrate but not dietary protein in lean rats.

Previous studies have shown that oral ingestion of nutrients stimulates secretion of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1); however, it is unclear whether there is a dose-dependent response between the amount of nutrient ingested and the secretion of the hormones in vivo. Using our lymph fistula rat model, we previously demonstrated that both GIP and GLP-1 responded dose dependently to increasing amounts of infused dietary lipid and that the GLP-1-secreting cells were more sensitive to changes in intestinal lipid content. In the present study, we investigated the dose-dependent relationships between incretin secretion and the two remaining macronutrients, carbohydrate and protein. To accomplish this objective, the major mesenteric lymphatic duct of male Sprague-Dawley rats was cannulated. Each animal received a single bolus (3 ml) of saline, dextrin, whey protein, or casein hydrolysate (0.275, 0.55, 1.1, 2.2, 4.4 kcal) via a surgically inserted duodenal or ileal feeding tube. Lymph was continuously collected for 3 h and analyzed for GIP and GLP-1 content. Both GIP and GLP-1 outputs responded dose dependently to increasing amounts of dietary carbohydrate but not protein. Additionally, we found that the GIP-secreting cells were more sensitive than the GLP-1-secreting cells to changes in intestinal carbohydrate content.

Nutriose, a prebiotic low-digestible carbohydrate, stimulates gut mucosal immunity and prevents TNBS-induced colitis in piglets.

BACKGROUND: We investigated a prebiotic low-digestible carbohydrate (LDC) as a possible food ingredient to stimulate bowel functions in the treatment of inflammatory bowel disease. The study aimed to assess a fermentable dextrin fiber (Nutriose) and its relationship to the immune management of the disease and the microbiota profile in colitis-bearing piglets. METHODS: In a randomized placebo-controlled parallel blind preclinical study, 32 male piglets were fed LDC (4% Nutriose) or dextrose placebo for 44 days before being challenged with trinitrobenzene sulfonic acid (TNBS) to induce colitis. We followed the microbiota profile using real-time polymerase chain reaction (PCR) targeted to 9 bacterial genera. Secretory IgA was evaluated by enzyme-linked immunosorbent assay (ELISA). Inflammatory protein profiles were monitored in blood and colonic tissues. Both histological scoring of biopsy samples and live endoscopic scoring were used to measure colitis development. RESULTS: Prior and continuing LDC supplementation alleviated the symptoms of colitis (body weight loss, bloody stools) induced by a TNBS challenge. This effect was associated with an improvement in endoscopic and histological scores. LDC was shown to selectively downregulate some of the proinflammatory factors and their concomitant pyretic events and to stimulate the Th2-related immune pathway (IL-10 and s-IgA). CONCLUSIONS: At the dose tested, LDC is a well-tolerated prebiotic agent able to not only stimulate butyrogenic bacteria strains and reduce intestinal transit disorders and energy intake, but also to prevent chronic inflammatory intestinal injuries.

Nutrient-driven incretin secretion into intestinal lymph is different between diabetic Goto-Kakizaki rats and Wistar rats.

The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) augment postprandial glucose-mediated insulin release from pancreatic beta-cells. The Goto-Kakizaki (GK) rat is a widely used, lean rodent model of Type 2 diabetes; however, little is known regarding the incretin secretion profile to different nutrients in these rats. We have recently shown that lymph is a sensitive medium to measure incretin secretion in rodents and probably the preferred compartment for GLP-1 monitoring. To characterize the meal-induced incretin profile, we compared lymphatic incretin concentrations in the GK and Wistar rat after enteral macronutrient administration. After cannulation of the major mesenteric lymphatic duct and duodenum, each animal received an intraduodenal bolus of either a fat emulsion, dextrin, a mixed meal, or saline. Lymph was collected for 3 h and analyzed for triglyceride, glucose, GLP-1, and GIP content. There was no statistical difference in GIP or GLP-1 secretion after a lipid bolus between GK and Wistar rats. Dextrin and a mixed meal both increased incretin concentration area under the curve, however, significantly less in GK rats compared with Wistar rats (dextrin GIP: 707 +/- 106 vs. 1,373 +/- 114 pg ml(-1) h, respectively, P < 0.001; dextrin GLP-1: 82.7 +/- 24.3 vs. 208.3 +/- 26.3 pM/h, respectively, P = 0.001). After administration of a carbohydrate-containing meal, GK rats were unable to mount as robust a response of both GIP and GLP-1 compared with Wistar rats, a phenomenon not seen after a lipid meal. We propose a similar, glucose-mediated incretin secretion pathway defect of both K and L cells in GK rats.

Safety profile of a food dextrin: acute oral, 90-day rat feeding and mutagenicity studies.

Nutriose is a glucose polysaccharide produced by the chromatographic separation of a dextrin fraction derived from maize, wheat or other edible starches. Animal safety studies conducted on Nutriose FB are reported. They include an acute oral and a 90-day study in rats and short-term in bacteria (Ames test) and a mutation assay at the TK locus in L5178Y mouse lymphoma cells. An acute oral study in Sprague-Dawley rats established the LD(50) as greater than 2000 mg/kg. In a 90-day, oral subchronic study, Sprague-Dawley rats were administered Nutriose FB in their diet at doses of 0, 1.25%, 2.5% or 5% for 13 weeks. Neither mortality nor significant behavioral changes occurred during the study. The consumption of Nutriose FB did not have any effect on body weight or on feed or water consumption. Blood coagulation and hematology and blood and urine biochemistry did not reveal any toxic effect of the compound. No treatment-related histopathological differences were observed between control and test groups. Adverse clinical observations, including ophthalmological observations, were marginal and not considered treatment-related. There was no effect of Nutriose FB on relative or absolute organ weight of rats of either sex, except for the increase in caecum content and caecum mucosa. The increase in caecum weight is considered a physiological adaptation seen after the ingestion of indigestible carbohydrates and is not considered a toxicological effect. The No-Observed-Adverse-Effect-Levels (NOAELs) were established by the highest tested doses: 4.4 g/kg bw/day in males and 6.5 g/kg bw/day in females. Mutation assays in bacteria (Ames tests) and in mammalian cells (tk locus in mouse lymphoma cells) were negative with Nutriose FB.

A dose-ranging phase I study of dextrin sulphate, a vaginal microbicide, in HIV-negative and HIV-positive female volunteers.

DESIGN: This phase I dose-ranging study of 2 weeks of twice-daily dextrin sulphate (DS), a sulphated polymer with in vitro activity against HIV, was designed in 2 parts. Part A was a randomized, placebo-controlled, double-blind, 3-arm trial (DS4%, DS1%, placebo) in HIV-negative women. In part B, HIV-positive women received DS4% and HIV-negative women were randomized to DS4% or no gel. RESULTS: One hundred women were enrolled from 2 sites (London and Antwerp): DS4% (n = 50, 20 of whom were HIV-positive), DS1% (n = 20), placebo (n = 10) and no gel (n = 20). There were no withdrawals related to adverse events and no cases of epithelial disruption. Spotting was reported by 24 women and numbers were significantly higher in all the gel groups (23 of 80), including placebo, compared with no gel (one of 20) (Fisher exact test P = 0.037). There was no evidence of a dose effect. Safety tests showed no evidence of systemic absorption. CONCLUSION: Although there was no clear explanation for the spotting, DS4% was well tolerated. It was decided to proceed with DS4% in an expanded safety study in Africa but to restrict entry to low-risk HIV-negative women, include a no-gel group, and monitor intermenstrual bleeding closely.

A randomized controlled safety and acceptability trial of dextrin sulphate vaginal microbicide gel in sexually active women in Uganda.

OBJECTIVE: To assess the safety of dextrin sulphate (DS) gel compared to placebo gel in terms of local and systemic adverse events, and to determine the acceptability of dextrin sulphate gel. DESIGN: A 4-week randomized trial of DS intra-vaginal gel, partially blinded, with placebo and observation control arms. Participants were randomized to use DS gel twice daily, placebo gel twice daily, DS gel pre-sex, or into an observation only arm. METHODS: Sexually active women were recruited from post natal and HIV clinics at Nsambya Hospital, Kampala, Uganda. Screening, enrollment and follow-up visits took place every 1 or 2 weeks over an 8-week period and consisted of questionnaire interviews, colposcopy examinations, sexually transmitted infection screen and routine laboratory testing. RESULTS: Out of a total of 172 women screened, 109 were randomized to use DS gel twice daily (65 women), placebo gel twice daily (15 women), DS gel pre-sex (nine women) or into an observation only arm (20 women). Two individuals had abnormal colposcopy findings in the DS twice daily gel use arm. Vaginal bleeding was reported as frequently by participants in the active gel arm as by participants in the placebo and observation only arms. No clinically significant difference was observed between arms in terms of vaginal flora, Candida, haemoglobin, white cell count, platelets, thrombin time, activated partial thromboplastin time, creatinine and aspartate aminotransferase results after 4 weeks of gel use. DS gel appeared to be acceptable to over 95% of the users. CONCLUSIONS: Results show a satisfactory safety and acceptability profile of dextrin sulphate gel.

Experience with the use of an iron polymaltose (dextrin) complex given by single total dose infusion to stable chronic haemodialysis patients.

BACKGROUND: Many studies of anaemia in patients on chronic haemodialysis have noted a high prevalence of iron deficiency despite oral iron supplementation. Our study examined the effect of intravenous iron given as bolus replacement. As the majority of these patients were not receiving concurrent recombinant human erythropoietin (rhEPO) it allowed an analysis of the safety and efficacy of intravenous iron as a single agent. METHODS: All patients with a haemoglobin level of less than 10 g/dl and considered iron deficient by the finding of a percentage transferrin saturation of less than 20% were given intravenous iron in the form of iron polymaltose (dextrin) by total dose infusion (TDI). The dose was calculated from tables supplied by the manufacturers. Patients with serum ferritin levels in excess of 225 ng/ml were excluded. RESULTS: In our unit, 62 out of 80 (77%) patients were considered iron deficient and received IV iron. Ten (10%) were considered to be in iron balance and 8 (10%) had biochemistry suggesting iron overload. None of the patients receiving iron experienced any adverse reactions. At three months a rise in haemoglobin level of at least 1 g/dl was noted in 53% of patients. The response was less in the remainder, but only 2 showed no response. CONCLUSIONS: Low levels of iron deficiency are often unrecognized in chronic haemodialysis patients on conventional therapy including oral iron supplementation. In such patients, the use of total dose infusion of iron polymaltose (dextrin) is a safe and effective method of raising haemoglobin levels. Substantial improvements may be achieved without the concurrent use of rhEPO.

Anti-Kaposi's sarcoma and antiangiogenic activities of sulfated dextrins.

Delivery of the sulfated polysaccharide dextrin 2-sulfate by the intraperitoneal route to the lymphatic circulation resulted in a clinically significant improvement in Kaposi's sarcoma in three patients. Our in vitro studies show that although sulfated dextrins do not interfere with the growth of isolated human umbilical vein endothelial cells, they do inhibit the morphological differentiation of endothelial cells into tubes as well as reduce new vessel formation in a placental angiogenesis assay. The antiangiogenic effect of dextrin 6-sulfate is greater than that of dextrin 2-sulfate and is independent of their anti-human immunodeficiency virus type 1 activities.

Reduction of the viral load of HIV-1 after the intraperitoneal administration of dextrin 2-sulphate in patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide, dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal route. DESIGN: An open Phase I/II dose-escalation clinical study in which six patients with AIDS were treated with seven courses of dextrin 2-sulphate each lasting 1 month. METHODS: During each course of treatment, the drug was administered daily for 28 days using an intraperitoneal catheter. Viral load was measured at frequent intervals using a plasma tissue culture infectious dose (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA. Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was completed without toxicity. A total of 7 patient-months of treatment were completed. With increasing doses of dextrin 2-sulphate, the infectious plasma viraemia, cellular viraemia and p24 antigenaemia all fell during the period of drug administration, but with no significant change in HIV-1 RNA. This was associated with increased plasma levels of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro. These beta-chemokines could have augmented the cell surface-mediated anti-HIV-1 effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine receptor-5. A second fall in infectious plasma viraemia, cellular viraemia, p24 antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for several months. A clinical improvement in Kaposi's sarcoma was also seen. CONCLUSIONS: Our results suggest that the intraperitoneal administration of dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS. With increasing doses of dextrin 2-sulphate, the fall in viral load was seen during the period of drug administration and again 2 months after completing treatment.