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Canine splenic hemangiosarcoma (HSA) is an aggressive tumour of vascular endothelium that carries a grave prognosis following standard of care treatment with surgery and doxorubicin. A previous pilot study revealed potential anti‐tumour activity of I'm‐Yunity polysaccharopeptide (PSP) for canine HSA. The aim of this prospective study was to assess patient outcome when treated with PSP alone or in combination with doxorubicin post‐splenectomy compared to patients treated with surgery and doxorubicin that received a placebo in place of PSP. Dogs undergoing splenectomy for splenic HSA were eligible. Following splenectomy, owners were offered treatment with PSP alone or adjuvant doxorubicin chemotherapy (unblinded). Patients with owners that selected to proceed with doxorubicin chemotherapy were blindly randomized to receive placebo or PSP. Dogs were evaluated weekly for 15 weeks, then scheduled for monthly visits until death. One hundred and one dogs were included in the final analysis: 51 PSP alone, 25 doxorubicin/placebo, and 25 combination PSP/doxorubicin. On multivariate analysis, dogs treated with single agent PSP, female dogs, decreased haematocrit at diagnosis, and stage III disease were negatively significantly associated with outcome; however, an interaction between treatment group and sex was documented. Gender‐specific outcomes revealed no significant difference in survival between treatment groups for male dogs, but female dogs treated with PSP alone had significantly reduced survival compared to females receiving doxorubicin/placebo (HR 0.21; p =.004). Anaemia (HR 5.28; p <.001) and stage III disease (HR 2.9; p =.014) remained negatively associated with survival when controlling for sex and treatment group. The addition of PSP to doxorubicin post‐splenectomy did not improve survival in dogs with splenic HSA. [ABSTRACT FROM AUTHOR]

Background: Acute graft-versus-host disease (aGVHD) is a severe and fatal complication after orthotopic liver transplantation (OLT). Clinical manifestations of severe aGVHD can resemble drug-induced Stevens– Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and there are also various medications, such as antibiotics and immunosuppressants, used after transplantation, causing a diagnostic dilemma. Furthermore, there have been no standardized diagnostic and therapeutic strategies for OLT-aGVHD due to its rarity. Case summary: A 52-year-old man presented with generalized maculopapular eruptions, fever, and pancytopenia 1 month after OLT and 4 days after taking sulfamethoxazole/trimethoprim. After assessment of the scoring criteria for drug causality of drug allergy, histopathological findings of skin biopsy, lymphocyte activation test of the potential offending drug, and microchimerism study, the diagnosis was in favor of aGVHD mimicking SJS/ TEN. Considering severe sepsis, the anti-tumor necrosis factor alpha (TNF-a) agent, etanercept, was used to replace tacrolimus and corticosteroid. Skin lesions resolved gradually after anti-TNF-a biologics rescue; tacrolimus and corticosteroid therapy were re-administrated after controlling sepsis. Pancytopenia recovered and the patient was discharged in a stable condition. Conclusion: We demonstrated a diagnostic strategy for OLT-aGVHD. Targeting therapy with anti-TNF-a blockade and a temporary withdrawal of traditional immunosuppressants may be among effective and safe therapeutic options of OLT-aGVHD for those with severe sepsis. [ABSTRACT FROM AUTHOR]

BackgroundAcute graft-versus-host disease (aGVHD) is a severe and fatal complication after orthotopic liver transplantation (OLT). Clinical manifestations of severe aGVHD can resemble drug-induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and there are also various medications, such as antibiotics and immunosuppressants, used after transplantation, causing a diagnostic dilemma. Furthermore, there have been no standardized diagnostic and therapeutic strategies for OLT-aGVHD due to its rarity.Case summaryA 52-year-old man presented with generalized maculopapular eruptions, fever, and pancytopenia 1 month after OLT and 4 days after taking sulfamethoxazole/trimethoprim. After assessment of the scoring criteria for drug causality of drug allergy, histopathological findings of skin biopsy, lymphocyte activation test of the potential offending drug, and microchimerism study, the diagnosis was in favor of aGVHD mimicking SJS/TEN. Considering severe sepsis, the anti-tumor necrosis factor alpha (TNF-α) agent, etanercept, was used to replace tacrolimus and corticosteroid. Skin lesions resolved gradually after anti-TNF-α biologics rescue; tacrolimus and corticosteroid therapy were re-administrated after controlling sepsis. Pancytopenia recovered and the patient was discharged in a stable condition.ConclusionWe demonstrated a diagnostic strategy for OLT-aGVHD. Targeting therapy with anti-TNF-α blockade and a temporary withdrawal of traditional immunosuppressants may be among effective and safe therapeutic options of OLT-aGVHD for those with severe sepsis.

Water-soluble Extract (WSE), also known as whey of goat milk yogurt contains many valuable constituents. The studies on biological activities of its constituent proteins have shown its activities as antimicrobial, antihypertensive, antioxidant, and immunomodulant. Experimental autoimmune thyroiditis can be induced by thyroid auto-antigens immunization which initiates the immune response, causing TH1 and Th17 cells infiltration, resulting in chronic inflammation and thyrocytes destruction. The present study hypothesized whether oral intake of goat milk yogurt WSE may represent an immunomodulatory effect in autoimmune thyroiditis (AITD) rats. Twenty female rats (Rattus norvegicus) were divided into five groups: healthy (A); AITD (B); and the AITD groups supplemented with various dose [300 (C); 600 (D); and 900 (E) mg/kg b.wt. per day] of goat milk yogurt WSE. The AITD rats were induced by a subcutaneous injection of 40 µg emulsion of dog's thyroglobulin and adjuvant (1:1) on day-0, -14, and -28. The supplementation of goat milk yogurt WSE was given orally for 28 days since the 35thday post-induction. The expression of IL-10 and IL-17 in the thyroid was analyzed by immunohistochemistry staining. The result showed that the supplementation of WSE significantly (P<0.05) increasing IL-10 expression and decreasing IL-17 in AITD rats. [ABSTRACT FROM AUTHOR]

Abstract Despite the extensive availability and use of plant extracts as feed additives in various livestock species, peer-reviewed and scientific evidence of their usage in horses is lacking. This article dealt with the review of reports from recent studies investigating the usage of plant bioactives or extracts in horse nutrition. For the time being, several herbs, either alone or in composites, are being commercialized and openly available in horsemarket stores, which makes it difficult and confusing for horse owners and veterinarians to make a justifiable choice. Usage of ginger extract as a feed additive in sport horses is encourageable as it manages to attain quick recovery after exhaustion in racing and jumping events. Garlic, ginseng, primerose, and rose hip possess potent antioxidative properties, and their supplementation in a regular diet may lessen the chance of occurrence of oxidative stress-related diseases. Owing to their cytoprotective and mucus-stimulatory effects, licorice and Aloe vera extracts have potentiality as feed additives in Standardbred and Thoroughbred racehorses, as they are more prone for equine gastric ulcer syndrome. Echinacea is able to stimulate the equine immunocompetence on addition to the regular diets of equine species. Besides the anti-inflammatory effect, devils claw possess anorexigenic effect, which can limit feed intake, thus keeping the body condition score in check and avoiding obese-related health problems in horses. Regularizing flaxseed meal or its extract as a dietary supplement may support healthy skin and coat condition due to the presence of omega-3 fatty acids as an active component. Aloe vera, well known for cytoprotective and mucus-stimulatory effects, is found to be efficient in protecting the gastrointestinal tract against ulcers or other disorders on administering as a dietary supplement to equines, but the extent of effect depends on the dosage and extent of supplementation. Although, theoretically plant extracts application is safer compared with synthetic antibiotics or drugs, it does not mean they are completely safe, and few considerations should be given for dosage of the drug, period of administration, apart from monitoring parallel drugs given to prevent herb-drug interactions. The plant extracts with potent benefits, and not tested in horses have to be evaluated with a primary objective to verify the negative side effects, if any, followed by standardization of the dosage. Highlights • Engaging plant extracts as feed additives is considered to be safe in equines. • Herbal extracts provide therapeutics and nutritional benefits effects to equines. • Plant extracts in regular diets may lessen the chances of stress-related disorders. • Herbal feed additives cannot be applied to horses due to the different susceptibility levels. • More research is required in adapting the dosage, period, and type of herb/plant or its extract. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to understand the effect of disease-modifying drugs (DMDs) on the long-term risk of multiple sclerosis (MS) disability and whether the effect is related to disability at start of treatment. It outlines an analysis of effect of therapy on progression to Expanded Disability Status Scale (EDSS) 3.0 and 6.0 using Cox regression analysis. The findings suggest that DMDs delayed long-term disability in MS patients in the later phase of the disease.

The main indication of cimetidine is being H 2-receptor antagonist, but studies suggest that cimetidine may also act as a non-specific stimulant of cell-mediated immunity and immunomodulator. In order to determine the immunomodulatory effect of dietary intake of cimetidine in the common carp (100 ± 10 g), subjects were fed diets containing 0 (control), 50, 100 and 200 mg cimetidine kg −1 of dry diet for a period of 6 weeks. TLC and NBT assays were significantly ( P < 0.05) stimulated in cimetidine-supplemented groups displaying the highest value in 200 mg kg −1 group. A decrease ( P < 0.05) in cortisol and ACH50 value was recorded in fish treated with cimetidine. Serum protein, albumin and serum globulin levels were not significantly changed. The findings of the present investigation suggest that the incorporation of cimetidine in the diet of common carp enhances the non-specific immunity. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies indicated that antimicrobial peptides (AMPs) play multiple roles in both innate and adaptive immune functions. The penaeidin of tiger shrimp Penaeus monodon shows an antimicrobial activity against Gram-positive bacteria and filamentous fungi. To study immunomodulation functions of the penaeidin, we transfected shrimp hemocytes in primary culture with penaeidin-specific small interfering RNA (siRNA-3) and observed a concomitant 20% reduction in adhesive hemocytes compared with mock-transfected cells. The addition of biosynthesized or chemically synthesized penaeidin or penaeidin proline-rich domain (PRD) to the culture medium of penaeidin knock-down hemocytes led to a full recovery in the number of adhesive hemocytes. The effect of penaeidin knock-down on the expression of tiger shrimp cell adhesion-associated molecules was examined using real-time Q-PCR. Results demonstrated 91% and 64% decreases in the expression of integrin-β and collagen, respectively, and a 396% increase in the expression of collagenase. The addition of chemically synthesized penaeidin after penaeidin knock-down hemocytes normalized the expression of these genes. The addition of the integrin-β ligand competitor RGDS to mock-transfected hemocytes decreased the number of adhesive hemocytes similar to penaeidin knock-down. In conclusion, penaeidin possesses an integrin-β-mediated cytokine feature that promotes shrimp granulocyte and semi-granulocyte adhesion. This is the first report about functional shrimp cytokine. [Copyright &y& Elsevier]

The article present case study of a 30-year-old obese woman with chronic migraine and generalized myasthenia gravis. Receiving concurrent treatment with a monoclonal antibody acting on the calcitonin gene-related peptide receptor (CGRPr) for migraine and with subcutaneous immunoglobulin (SCIg) for myasthenia gravis (MG).

In recent years immunomodulators have gained a strong interest and represent nowadays an active expanding area of research for the control of microbial diseases and for their therapeutic potential in preventing, treating and reducing the morbidity and mortality of different diseases. Pidotimod (3-L-pyroglutamyl-L-thiaziolidine-4carboxylic acid, PDT) is a synthetic dipeptide, which possesses immunomodulatory properties and exerts a well-defined pharmacological activity against infections, but its real mechanism of action is still undefined. Here, we show that PDT is capable of activating tyrosine phosphorylation-based cell signaling in human primary monocytes and triggering rapid adhesion and chemotaxis. PDT-induced monocyte migration requires the activation of the PI3K/Akt signaling pathway and chemokine receptor CXCR3. Indeed, a mAb to CXCR3 and a specific receptor inhibitor suppressed significantly PDT-dependent chemotaxis, and CXCR3-silenced primary monocytes lost responsiveness to PDT chemoattraction. Moreover, our results highlighted that the PDT-induced migratory activity is sustained by the CXCR3A isoform, since CXCR3-transfected L1.2 cells acquired responsiveness to PDT stimulation. Finally, we show that PDT, as CXCR3 ligands, is also able to direct the migration of IL-2 activated T cells, which express the highest levels of CXCR3 among CXCR3-expressing cells. In conclusion, our study defines a chemokine-like activity for PDT through CXCR3A and points on the possible role that this synthetic dipeptide may play in leukocyte trafficking and function. Since recent studies have highlighted diverse therapeutic roles for molecules which activates CXCR3, our findings call for an exploration of using this dipeptide in different pathological processes. [ABSTRACT FROM AUTHOR]