Comparison of water- and alkali-extracted polysaccharides from Fuzhuan brick tea and their immunomodulatory effects in vitro and in vivo.

In the present study, the purpose is to compare the effect of water extraction and alkali-assisted extraction on the structural characteristics and immunomodulatory activity of polysaccharides from Fuzhuan brick tea (FBTPs). The results indicated that water-extracted FBTPs (W-FBTPs) and alkali-extracted FBTPs (A-FBTPs) had similar molecular weights but different monosaccharide compositions, of which A-FBTPs had a higher yield and uronic acid groups corresponding to galacturonic acid (GalA). Moreover, A-FBTPs had stronger ability to promote phagocytic capacity, acid phosphatase activity and nitric oxide (NO) secretion in macrophages in vitro. In the in vivo study, A-FBTPs exhibited a promising effect to adjust the immune imbalance by enhancing the body features, antioxidant activities, immune response and intestinal mucosal barrier in cytoxan (CTX)-induced immunosuppressive mice. Besides, A-FBTP supplementation effectively improved CTX-induced gut microbiota dysbiosis, including promoting the abundance of beneficial bacteria (e.g., Lactobacillus) and short chain fatty acid (SCFA)-producing bacteria (e.g., Lachnospiraceae, Prevotellaceae and Ruminococcaceae), along with reducing the growth of potentially pathogenic microbes (e.g., Desulfovibrionaceae and Helicobacter). These findings suggested that alkaline extraction might be a promising way to obtain high-quality acidic polysaccharides from Fuzhuan brick tea (FBT), and A-FBTPs could be developed as novel potential prebiotics and immunomodulators for further application in food formulations.

The immunoenhancement effects of sea buckthorn pulp oil in cyclophosphamide-induced immunosuppressed mice.

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines. In addition, SBT pulp oil can promote the production of short fatty acids (SCFAs), increase the diversity of gut microbiota, improve the composition of intestinal flora, increase the abundance of Alistipes, Bacteroides, Anaerotruncus, Lactobacillus, ASF356, and Roseburia, while decreasing the abundance of Mucispirillum, Anaeroplasma, Pelagibacterium, Brevundimonas, Ochrobactrum, Acinetobacter, Ruminiclostridium, Blautia, Ruminiclostridium, Oscillibacter, and Faecalibaculum. This study shows that SBT pulp oil can regulate the diversity and composition of intestinal microflora in CTX-induced immunosuppressive Balb/c mice, thus enhancing the intestinal mucosa and systemic immune response. The results can provide a basis for understanding the function of SBT pulp oil and its application as a new probiotic and immunomodulator.

Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment.

Cancer immunotherapy can boost the immune response of patients to eliminate tumor cells and suppress tumor metastasis and recurrence. However, immunotherapy resistance and the occurrence of severe immune-related adverse effects are clinical challenges that remain to be addressed. The tumor microenvironment plays a crucial role in the therapeutic efficacy of cancer immunotherapy. Injectable hydrogels have emerged as powerful drug delivery platforms offering good biocompatibility and biodegradability, minimal invasion, convenient synthesis, versatility, high drug-loading capacity, controlled drug release, and low toxicity. In this review, we summarize the application of injectable hydrogels as a unique platform for targeting the immunosuppressive tumor microenvironment.

The use of nanoparticles as alternative therapeutic agents against Candida infections: an up-to-date overview and future perspectives.

Candida spp. are opportunistic fungi that can cause severe infections especially in immunocompromised patients. Candidiasis is currently the most frequent fungal disease affecting humans globally. This rise is attributed to the vast increase in resistance to antifungal agents. In recent years, the epidemiological and clinical relevance of fungal infections caused by Candida species have attracted a lot of interest with increasing reports of intrinsic and acquired resistance among Candida species. Thus, the formulation of novel, and efficient therapy for Candida infection persists as a critical challenge in modern medicine. The use of nanoparticle as a potential biomaterial to achieve this feat has gained global attention. Nanoparticles have shown promising antifungal activity, and thus, could be seen as the next generation antifungal agents. This review concisely discussed Candida infection with emphasis on anti-candida resistance mechanisms and the use of nanoparticles as potential therapeutic agents against Candida species. Moreover, the mechanisms of activity of nanoparticles against Candida species, recent findings on the anti-candida potentials of nanoparticles and future perspectives are also presented.

Activity of ceftolozane-tazobactam and comparators when tested against bacterial surveillance isolates collected from patients at risk of infections caused by resistant gram-negative pathogens.

Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a ß-lactamase inhibitor. Ceftolozane-tazobactam has been approved for treatment of complicated urinary tract infections and acute pyelonephritis, for complicated intra-abdominal infections (with metronidazole) in adults, and for hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia. This study analyzed gram-negative pathogen susceptibility in US and European patients who are considered at risk for infections caused by pathogens resistant to commonly used antimicrobials: patients in the intensive care unit (ICU), patients on the hematology/oncology or transplant service who may be immunocompromised, and patients >65 years old (yo). ICU patients had the lowest susceptibility for Enterobacterales and PSA. The susceptibility for isolates from the immunocompromised and >65 yo groups was similar. Ceftolozane-tazobactam was the most active agent against PSA, with ≥90%S for >65 yo and immunocompromised, and >80%S for ICU. Meropenem and ceftolozane-tazobactam were the most active agents against Enterobacterales.

[Functional immunoassays in the setting of infectious risk and immunosuppressive therapy of non-HIV immunocompromised patients]. / Place des tests immunitaires fonctionnels dans la prise en charge du risque infectieux et de la gestion des thérapies immunosuppressives chez les patients immunodéprimés non-VIH.

The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.

Components identification and nutritional value exploration of tea (Camellia sinensis L.) flower extract: Evidence for functional food.

Camellia sinensis L., its fresh leaves and buds are used to make tea, is an important industrial crop with a long history. However, less attention has been paid to tea flowers. Indeed, tea flower extract (TFE) is a rich source of functional molecules, but its nutritional value remains unclear. This study, from the perspective of "whole food", aimed to investigate the composition of TFE and further explore its possible health-promoting effects on cyclophosphamide-induced mice. It was found that TFE was mainly composed of carbohydrates (34.02 ± 1.42%), phenolic compounds (11.57 ± 0.14%), crude proteins (27.72 ± 3.07%) and saponins (2.81 ± 0.00%). Supplementation of TFE at 200 mg/kg·BW/d regulated intestinal homeostasis by improving the intestinal barrier, alleviating dysbacteriosis (reverse 44 of 68 disordered genera), stimulated immunoreactions with significant enhancement of serum TNF-α, IFN-γ, IL-1ß, IL-2 and IL-6. Furthermore, TFE could improve the liver function through decreasing the hepatic malondialdehyde and aminotransferase levels and increasing the levels of catalase, myeloperoxidase, superoxide dismutase and reduced glutathione. Notably, the ameliorating effects of TFE on cyclophosphamide-induced immunosuppression and the hepatic injury were associated with its modulation of gut microbiota. The results provide the evidence for the application of tea flower as potential functional food.

Immunomodulatory Activities of Polysaccharides from White Button Mushroom, Agaricus bisporus (Agaricomycetes), Fruiting Bodies and Cultured Mycelia in Healthy and Immunosuppressed Mice.

Agaricus bisporus is a very important edible and medicinal mushroom. In this study, we systematically investigated the monosaccharide composition, methylation, and immunomodulatory activities of polysaccharides from A. bisporus fruiting bodies (FPS), cultured mycelia (IPS), and fermentation broth (EPS). The results indicated that FPS was mainly composed of mannose; IPS, of glucose; and EPS, of galactose. However, the methylation results indicated that FPS, IPS, and EPS possessed different polysaccharide structures. Furthermore, FPS, IPS, and EPS caused remarkable increases in the thymus and spleen indexes; in the amounts of serum cytokines containing interleukin (IL)-2, IL-4, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ); in the counts of CD3+CD4+ lymphocytes and the ratio of CD4+ to CD8+ T lymphocytes; however, they decreased the counts of CD3+CD8+ lymphocytes in normal mice. Finally, in cyclophosphamide-treated mice, the FPS, IPS, and EPS were able to significantly restore the thymus and spleen indexes, lymphocyte proliferation, phagocytotic activity of peritoneal macrophages, and levels of IL-2, IL-6, IL-10, IL-17, TNF-α, and immunoglobin G. These findings suggest that FPS, IPS, and EPS could all be exploited as immunomodulatory agents and potential immunotherapeutic medicines for patients with inadequate immune function.

Orostachys japonicus A. Berger Extracts Induce Immunity-Enhancing Effects on Cyclophosphamide-Treated Immunosuppressed Rats.

In this study, we evaluated the immunity-enhancing effects of Orostachys japonicus A. Berger (OJ). To examine the immune protective effect in vitro, primary mouse splenocytes were treated with water or ethanol extracts of OJ in the absence or presence of cyclophosphamide (CY), which is a cytotoxic, immunosuppressive agent. The extracts increased the propagation of splenocytes and inhibited CY-induced cytotoxicity. Further, to examine the immunostimulatory effects in vivo, adult Wistar rats were orally administered OJ extracts with or without CY treatment. With the administration of OJ extracts, CY-treated immunosuppressed rats showed improved physical endurance, as assessed by the forced swim test. In addition, extract administration increased not only the number of immunity-related cells but also the levels of plasma cytokines. OJ extracts also recovered splenic histology in CY-treated rats. These findings suggest that an OJ regimen can enhance immunity by increasing immune cell propagation and specific plasma cytokine levels.

Immunomodulatory activity of a novel polysaccharide from Lonicera japonica in immunosuppressed mice induced by cyclophosphamide.

Lonicera japonica is a typical Chinese herbal medicine. We previously reported a method to isolate polysaccharides from Lonicera japonica (LJP). In this study, we first performed a qualitative analysis of LJP using the Fourier Transform Infrared Spectrometer (FT-IR) and explored the monosaccharide composition of LJP using the pre-column derivatization high performance liquid chromatography (HPLC) method. We then investigated the immunomodulatory function of LJP in cyclophosphamide (CTX)-induced immunosuppressed mouse models. The results showed that LJP had the characteristic absorption of typical polysaccharides consisting of 6 types of monosaccharides. In addition, LJP can increase significantly the organ index, splenic lymphocyte proliferation, macrophage phagocytosis, and natural killer (NK) cell activity in CTX-treated mice. LJP could also restore the levels of serum cytokines interleukin (IL-2), tumor necrosis factor (TNF-α) and Interferon-γ (IFN-γ) in the CTX-treated mice. Finally, the results on measuring the T-lymphocytes subsets of spleen also confirmed LJP-induced immunomodulatory activity in immunosuppressed mice from another perspective. Therefore, LJP could be used as a potential immunomodulatory agent.

In vitro toxicity and efficacy of verdinexor, an exportin 1 inhibitor, on opportunistic viruses affecting immunocompromised individuals.

Infection of immunocompromised individuals with normally benign opportunistic viruses is a major health burden globally. Infections with viruses such as Epstein-Barr virus (EBV), human cytomegalovirus (HCMV), Kaposi's sarcoma virus (KSHV), adenoviruses (AdV), BK virus (BKPyV), John Cunningham virus (JCPyV), and human papillomavirus (HPV) are significant concerns for the immunocompromised, including when these viruses exist as a co-infection with human immunodeficiency virus (HIV). These viral infections are more complicated in patients with a weakened immune system, and often manifest as malignancies resulting in significant morbidity and mortality. Vaccination is not an attractive option for these immune compromised individuals due to defects in their adaptive immune response. Verdinexor is part of a novel class of small molecules known as SINE (Selective Inhibitor of Nuclear Export) compounds. These small molecules demonstrate specificity for the nuclear export protein XPO1, to which they bind and block function, resulting in sequestration of XPO1-dependent proteins in the nucleus of the cell. In antiviral screening, verdinexor demonstrated varying levels of efficacy against all of the aforementioned viruses including previously with HIV. Studies by other labs have discussed likely mechanisms of action for verdinexor (ie. XPO1-dependence) against each virus. GLP toxicology studies suggest that anti-viral activity can be achieved at a tolerable dose range, based on the safety profile of a previous phase 1 clinical trial of verdinexor in healthy human volunteers. Taken together, these results indicate verdinexor has the potential to be a broad spectrum antiviral for immunocompromised subjects for which vaccination is a poor option.

Epidemiology, treatment and prevention of herpes zoster: A comprehensive review.

Herpes zoster is a major health burden that can affect individuals of any age. It is seen more commonly among individuals aged ≥50 years, those with immunocompromised status, and those on immunosuppressant drugs. It is caused by a reactivation of varicella zoster virus infection. Cell-mediated immunity plays a role in this reactivation. Fever, pain, and itch are common symptoms before the onset of rash. Post-herpetic neuralgia is the most common complication associated with herpes zoster. Risk factors and complications associated with herpes zoster depend on the age, immune status, and the time of initializing treatment. Routine vaccination for individuals over 60 years has shown considerable effect in terms of reducing the incidence of herpes zoster and post-herpetic neuralgia. Treatment with antiviral drugs and analgesics within 72 hours of rash onset has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia. This study mainly focuses on herpes zoster using articles and reviews from PubMed, Embase, Cochrane library, and a manual search from Google Scholar. We cover the incidence of herpes zoster, gender distribution, seasonal and regional distribution of herpes zoster, incidence of herpes zoster among immunocompromised individuals, incidence of post-herpetic neuralgia following a zoster infection, complications, management, and prevention of herpes zoster and post-herpetic neuralgia.

Comparison of three cell-based drug screening platforms for HSV-1 infection.

Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

Immunomodulatory and Antioxidant Effects of Polysaccharides from Gynostemma pentaphyllum Makino in Immunosuppressed Mice.

The immunomodulatory and antioxidant activities of crude polysaccharides extracted from Gynostemma pentaphyllum Makino (GPMPP) were investigated. GPMPP was composed of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.39:3.76:1.00:1.64:4.98:5.88. In vivo studies showed GPMPP significantly increased the spleen and thymus indices, activated the macrophage phagocytosis and NK cells, and exhibited activity on none or Con A/LPS-stimulated splenocytes in a dose-dependent manner in C57BL/6 mice. Moreover, GPMPP elevated CD4⁺ T lymphocyte counts as well as the CD4⁺/CD8⁺ ratio dose-dependently, and it increased IL-2 level in the sera and spleen of Cy-immunosuppressed mice. Furthermore, GPMPP significantly increased the SOD, GSH-Px, T-AOC, GSH and CAT level, and decreased the MDA level. The results showed that GPMPP might play an important role in prevention of oxidative damage in immunological system. These findings indicate GPMPP has immunomodulatory activity in vivo and seems to be an effective natural immunomodulatory agent.

Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats.

The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL-12, and tumor necrosis factor-α (TNF-α) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide-associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the α-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression.

[Generation of Antibiotic Tolerant Bacterial Persisters in Immunocompromized Patients with Hematologic and Malignant Diseases: A New Problem of Health-Care Associated Infections].

Background: Antibiotic tolerance (AT) represents one of the causes of the phenomenon of antibiotic resistance that allows escape of non-replicating metabolically inert microorganisms (persisters) from any antibiotics attack because molecular targets of antibiotics are lacking thereby creating the potential for chronic infections. Aims: Determine the heterogeneity of the strains of opportunistic pathogens E. coli and P. aeruginosa isolates from children with hematologic malignancies containing bacterial persisters that cause the AT phenomenon. Methods: Children with hematological malignancies were divided into 2 groups according to the intensity of antibiotic treatment of infectious complications. Ciprofloxacin-induced persisters were quantitatively determined in the biological materials obtained from sick children. Results: Within the clinical isolates of E. coli and P. aeruginosa, about a third of the strains belong to high-persisting. The numbers of persistent forms of bacteria did not correlate with a minimal inhibitory concentration values ciprofloxacin (r=0.148, n=25, p>0.05). Interestingly, higher level of formation of persistent E. coli and P. aeruginosa, is associated with higher frequencies of infection attacks, massive antibiotic use and unfavorable course of the disease in children. Conclusions: Therefore, detecting the persistent forms of bacterial pathogens including those associated with the health-care associated infection, specifically, in immunocompromised patients, should be included into the contemporary algorithms of microbiological observation and monitoring of patients and intrahospital environment.

Infections Caused by Rapidly Growing Mycobacteria spp in Children and Adolescents With Cancer.

BACKGROUND: Rapidly growing mycobacteria (RGM) infections in pediatric oncology patients have not been completely characterized. METHODS: We reviewed medical records of oncology patients at St. Jude Children's Research Hospital (St. Jude) from 1990 to 2010 with RGM infections and summarized the results of previously published cases. RESULTS: Twenty-five St. Jude patients had 27 episodes of infection. Approximately half of the cases occurred in patients with hematological malignancies and in males; infections were more common in white patients. Most patients were not neutropenic or lymphopenic. The most common causative species were Mycobacterium chelonae, Mycobacterium abscessus, and Mycobacterium fortuitum. Most isolates were susceptible to amikacin and clarithromycin; all were susceptible to at least 1 of these. Treatment regimens varied considerably, particularly with respect to the duration of antimicrobial chemotherapy. Two St. Jude patients died; both had pulmonary infections. The literature search identified an additional 58 cases of infection. Localized catheter-associated infections were more common than bloodstream infections in the current series than in previous reports, and outbreaks were not recognized. Otherwise, the demographic and clinical characteristics of patients were similar. CONCLUSIONS: Localized catheter-associated infections were most common in this largest reported single center experience reported to date. Pulmonary infection is uncommon in children but, as in adults, has a high mortality rate. Relatively short-term antimicrobial treatment and surgical debridement of infected tissue, if present, may be as effective for catheter-associated infections as prolonged antimicrobial use and may reduce adverse drug effects in these patients, who are vulnerable to drug-drug interactions and toxicity.

Bioactive components on immuno-enhancement effects in the traditional Chinese medicine Shenqi Fuzheng Injection based on relevance analysis between chemical HPLC fingerprints and in vivo biological effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenqi Fuzheng Injection (SFI) is an injectable traditional Chinese herbal formula comprised of two Chinese herbs, Radix codonopsis and Radix astragali, which were commonly used to improve immune functions against chronic diseases in an integrative and holistic way in China and other East Asian countries for thousands of years. MATERIALS AND METHODS: This present study was designed to explore the bioactive components on immuno-enhancement effects in SFI using the relevance analysis between chemical fingerprints and biological effects in vivo. According to a four-factor, nine-level uniform design, SFI samples were prepared with different proportions of the four portions separated from SFI via high speed counter current chromatography (HSCCC). SFI samples were assessed with high performance liquid chromatography (HPLC) for 23 identified components. For the immunosuppressed murine experiments, biological effects in vivo were evaluated on spleen index (E1), peripheral white blood cell counts (E2), bone marrow cell counts (E3), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7). Based on the hypothesis that biological effects in vivo varied with differences in components, multivariate relevance analysis, including gray relational analysis (GRA), multi-linear regression analysis (MLRA) and principal component analysis (PCA), were performed to evaluate the contribution of each identified component. RESULTS: The results indicated that the bioactive components of SFI on immuno-enhancement activities were calycosin-7-O-ß-d-glucopyranoside (P9), isomucronulatol-7,2'-di-O-glucoside (P11), biochanin-7-glucoside (P12), 9,10-dimethoxypterocarpan-3-O-xylosylglucoside (P15) and astragaloside IV (P20), which might have positive effects on spleen index (E1), splenic lymphocyte proliferation (E4), splenic natural killer cell activity (E5), peritoneal macrophage phagocytosis (E6) and the amount of interleukin-2 (E7), while 5-hydroxymethyl-furaldehyde (P5) and lobetyolin (P13) might have negative effects on E1, E4, E5, E6 and E7. Finally, the bioactive HPLC fingerprint of SFI based on its bioactive components on immuno-enhancement effects was established for quality control of SFI. CONCLUSIONS: In summary, this study provided a perspective to explore the bioactive components in a traditional Chinese herbal formula with a series of HPLC and animal experiments, which would be helpful to improve quality control and inspire further clinical studies of traditional Chinese medicines.

Gut-targeted immunonutrition boosting natural killer cell activity using Saccharomyces boulardii lysates in immuno-compromised healthy elderly subjects.

The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to healthy volunteers (65-79 years) previously selected for low natural killer (NK) cell activity, and this parameter was checked at the completion of the study. A significant improvement in NK cell activity of KC-1317 consumers was observed as compared to placebo at the end of 2 months. Although preliminary, these beneficial immune-modulatory effects of KC-1317 in aged individuals might indicate its employment within a wider age-management strategy.

Voriconazole serum concentrations in obese and overweight immunocompromised patients: a retrospective review.

STUDY OBJECTIVE: To evaluate the relationship between voriconazole dose and corresponding serum concentrations in obese and overweight immunocompromised patients. DESIGN: Retrospective medical record review. SETTING: National Cancer Institute-designated comprehensive cancer center. PATIENTS: A total of 92 patients with hematologic malignancies and/or hematopoietic stem cell transplants who received voriconazole and had reported steady-state serum concentrations (peak, random, or trough) during 2005-2010; 124 serum concentrations were available for analysis. MEASUREMENTS AND MAIN RESULTS: Data on patient demographics, voriconazole concentrations, and other clinical and safety data were collected. Patients were stratified based on body mass index (BMI). Patients with higher BMIs tended to have significantly higher median random voriconazole concentrations with intravenous administration (6.4 mg/L for BMI ≥ 25 kg/m(2) vs 2.8 mg/L for BMI < 25 kg/m(2), p=0.04). This trend was more notable with the intravenous than the oral formulations. With the oral formulation, patients with a BMI of 25 kg/m(2) or greater had a median random concentration of 2.8 mg/L compared with 2.0 mg/L in patients with a BMI less than 25 kg/m(2) (p=0.18). Patients with a BMI of 25 kg/m(2) or greater also had a higher median daily voriconazole dose (640 vs 400 mg, p<0.001). No significant differences were noted in factors that would affect oral absorption of voriconazole (e.g., graft-versus-host disease) among BMI groups. When comparing all voriconazole concentrations, higher concentrations were associated with a greater percentage of patients who had alanine aminotransferase levels of more than 3 times the upper limit of normal. Patients with voriconazole random concentrations of 2 mg/L or greater had higher response rates (50%) than patients with concentrations lower than 2 mg/L (33%). CONCLUSION: Standard voriconazole dosing using actual body weight in obese and overweight patients resulted in higher associated serum concentrations. Dosing using adjusted body weight may be necessary in this population in order to achieve optimal concentrations while preventing the potential for increased toxicity.