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Ronak Ahmed,1 Dana Sharif,2 Mohammad Jaf,1,3 Dashty Mohammed Amin3 1Dermatology Unit, College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq; 2Department of Medicine, College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq; 3Medical Laboratory Science, KOMAR University of Science and Technology, Sulaymaniyah, Iraq; 4Kurdistan Board of Dermatology, Kurdistan Board for Medical SpecializationCorrespondence: Ronak AhmedDermatology Unit, College of Medicine, University of Sulaimani, Sulaymaniyah, IraqTel +9647501176757Email dr-ronaksa@hotmail.comBackground: Vitiligo is a chronic acquired pigmentary disorder of the skin; it results from immunological distruction of functioning melanocytes. The cytokine TNF-α plays a central role in the initiation of melanocyte apoptosis in vitiligo. Single nucleotide polymorphism (SNP) in the promoter region of the gene coding for serum TNF-α may affect its production.Objective: The aim of this study is to assess serum TNF-α as a risk factor for generalized vitiligo among Iraqi patients and to rule out that polymorphism at the − 308 position affects serum TNF-α.Materials and Methods: This case–control study was conducted at Sulaymaniyah Dermatology Teaching Center (SDTC), Iraq. Serum concentration of TNF-α was measured using enzyme linked immunosorbent assay (ELISA) technique in 80 patients with generalized vitiligo and 40 clinically healthy controls. The amplification refractory mutation system polymerase chain reaction (ARMS–PCR) technique was used for detection of TNF-308G/A gene polymorphism. TNF-α level correlated with TNF- 308G/A gene polymorphism. Serum concentration and TNF -308G/A gene polymorphism have been analyzed in correlation with demographic features and clinical characteristics of patients with generalized vitiligo.Results: Statistically significant elevation of serum TNF-α seen in patients compared to a control group (p-value 0.01). Significantly higher TNF-α level (p-value 0.01) found among patients with active generalized vitiligo. Elevated serum levels of TNF-α were significantly associated with both TNFA1 (TNF-308G) allele (p-value 0.04) and TNFA2 (TNF-308A) allele (p-value 0.03). TNF-α − 308GA polymorphism was not affected by demographic features and clinical characteristics of patients with generalized vitiligo.Conclusion: TNF-α in the serum is a risk factor for generalized vitiligo among Iraqi patients. Patients with active vitiligo have a higher serum TNF-α level. No difference was found between serum level of TNF-α with TNF-α polymorphism at position − 308 (TNF − 308). This involves substituting G allele for the A allele.Keywords: generalized vitiligo, serum TNF-α − 308G/A promoter polymorphism, Iraq

Sergliflozin, the active entity of sergliflozin etabonate, is a selective inhibitor of sodium-dependent glucose cotransporter 2 (SGLT2). The pharmacokinetics and pharmacodynamics of sergliflozin were evaluated following single oral dose administration of sergliflozin etabonate (5-500 mg) in healthy volunteers (n = 22) and patients with type 2 diabetes mellitus (n = 8). The prodrug was rapidly and extensively converted to sergliflozin; the latter displayed linear kinetics, reached maximum plasma concentrations at approximately 30 to 45 minutes postdose (t(max)), and had a plasma elimination half-life (t(1/2)) of ~0.5 to 1 hour. Both prodrug and active entity showed low glomerular filtration and/or extensive renal tubular reabsorption, with <0.5% of the administered dose being recovered in the urine. In both populations, sergliflozin etabonate produced a dose-related glucosuria under fasting conditions and following glucose loading but did not appreciably affect urinary electrolyte excretion or fluid balance. The magnitude and duration of the glucosuric effect closely paralleled plasma sergliflozin concentrations. Sergliflozin did not significantly affect fasting plasma glucose levels but produced transient attenuation of the plasma glucose AUC following glucose challenge. Single doses of sergliflozin etabonate 5 to 500 mg were well tolerated, and there were no clinically significant adverse laboratory findings. [ABSTRACT FROM AUTHOR]

Introduction: The incidence rate of newly diagnosed HIV infection in Indonesia decreased from 21 per 100,000 in 2011 to 10 per 100,000 in 2021. Despite this progress, AIDS-related deaths among people living with HIV (PLWH) increased from 3.4% in 2010 to 4.8% in 2020. Determining risk factors for mortality may identify areas to intervene and reduce mortality., Methods: A multicenter, prospective, observational cohort study of HIV infection, coinfections, and comorbidities (INA-PROACTIVE) was carried out at 19 hospitals across major islands in Indonesia. The study enrolled PLWH from 2018-2020 and followed them for 3 years. For this analysis, PLWH ≥ 18 years old with one year of follow-up data were included. Cox regression was used to identify variables at enrollment that correlated with one-year mortality., Results: Among the 4,050 PLWH analysed in the study, 68.8% were male, 53.5% acquired HIV through heterosexual transmission, 92.4% were on antiretroviral treatment (ART) at enrollment, and 72.4% had an undetectable viral load. At one year, 115 (2.8%) had died. Detectable viremia at enrollment was significantly associated with mortality, with the risk increasing as the viral load (VL) category increased (adjusted hazard ratio [aHR] 4.47, 95% CI: 1.47-13.56 for VL 50 to < 1,000 copies/mL; aHR 7.88, 95% CI: 2.80-22.20 for VL 1,000 to 10,000 copies/mL; and aHR 18.33, 95% CI: 7.94-42.34 for VL > 10,000 copies/mL; compared to VL < 50 copies/mL). Other factors at enrollment significantly associated with mortality were a CD4 + count < 200 (aHR 8.02, 95% CI: 2.69-23.86; compared to ≥ 350), age 40-49 years (aHR 2.19, 95% CI 1.23-3.87; compared to 18-29 years) and being underweight (aHR 1.84, 95% CI: 1.18-2.85; compared to normal weight)., Conclusions: Among predominantly treatment-experienced PLWH, detectable viremia and continued immunosuppression were significantly associated with one-year mortality. This study highlights the importance of ART with complete viral suppression as well as immune recovery to prevent mortality., Trial Registration: Clinical Trial Number: NCT03663920, registration date: 4 January 2018., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was reviewed and approved by the central Ethics Committee of the National Institute of Health Research and Development (NIHRD) (LB.02.01/2/KE.012/2018) and the Ethics Committees of 2 study sites requiring additional reviews. All participants or their guardians signed informed consent to participate in the study, with minors signing assent as appropriate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood., Objectives: The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex., Methods: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, β-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, β-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination., Results: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and β-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, β-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and β-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups., Conclusion: blocking α- and/or β-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on β-arrestin2 levels in the cerebral cortex., (© 2023. The Author(s).)

In breast cancer, there has been evidence of atypical activation of signal transduction and activators of transcription 3 (STAT3). Thymoquinone (TQ) exerts its anti-neoplastic effect through diverse mechanisms, including STAT3 inhibition. The tumor suppressor, microRNA-125a-5p was reported to be downregulated in various breast cancer cells. Therefore, we investigated the influence of TQ and/or doxorubicin on microRNA-125a-5p and its correlation with STAT3 activation as well as tumor growth in mice bearing solid Ehrlich tumors. We found that TQ markedly suppressed inducible and constitutive phosphorylation of STAT3 in tumor tissue without affecting STAT5. Moreover, it attenuated tumor growth, downregulated STAT3 downstream target proteins, and increased the apoptotic activities of caspase-3 and -9. Interestingly, TQ-elicited synergism of doxorubicin anti-neoplastic activity was coupled with upregulation of tumoral microRNA-125a-5p. Taken together, the current findings raise the potential of TQ as a promising chemomodulatory adjuvant to augment mammary carcinoma sensitivity to doxorubicin., (© 2021 Wiley Periodicals LLC.)

Background and Aim: Lumpy skin disease (LSD) is a contagious viral disease that has great economic losses among Egyptian breeding flocks. The present study was designed to compare the results of different diagnostic approaches used for the diagnosis of LSD virus (LSDV)., Materials and Methods: A total of 73 skin nodule samples were collected from suspected infected cattle with LSDV from some Egyptian governorates during 2019 and 2020. Trials for virus isolation (VI) and identification on embryonated chicken eggs (ECEs) were conducted. Molecular detection, histopathological, and immunohistochemical examination were also conducted., Results: The virus was isolated into ECEs, and 58 samples of 73 were positive and gave a characteristic pock lesion on the chorioallantoic membrane. Twenty-two representative nodular skin specimens of the 58 positive samples were selected to be used for molecular, histopathological, and immunohistochemistry (IHC) diagnosis. Conventional polymerase chain reaction succeeded in detecting LSDV DNA in all tested 22 skin nodule samples. Histological examination of skins of different cases revealed various alterations depending on the stage of infection. IHC was used as a confirmatory test for detecting LSDV antigen in the tissues of the skin nodules of infected cattle using specific anti-LSDV antibodies. Lumpy skin viral antigen was detected within the cytoplasm of the epidermal basal cells layer and prickle cell and within the cytoplasm of the hair follicles' epithelial outer and inner roots., Conclusion: This study confirmed the prevalence of LSDV infection in different Egyptian governorates during 2019 and 2020. In addition, histopathology and IHC could be potential methods to confirm Lumpy skin disease infection besidesVI and molecular detection., (Copyright: © Amin, et al.)

Purpose: Many cytokines have been implicated in the pathogenesis of psoriasis, among these the transforming growth factor-beta 1 (TGF-β1) can be endorsed by different mechanisms besides inhibiting keratinocytes proliferation. The role of genetic polymorphisms of TGF-β1 has been studied in various inflammatory diseases. Our aim is to study the correlation of TGF-β1 gene polymorphism at codon 10 and 25 with the expression of serum level of TGF-β1 in a sample of Iraqi psoriatic patients compared to the control group., Materials and Methods: A cross-sectional study involved 100 patients with psoriasis vulgaris and 50 sex- and age-matched healthy volunteers as control group. Serum and genomic DNA were prepared from peripheral blood samples. Amplification refractory mutation system-polymerase chain reaction technique (ARMS-PCR) had been applied for genotyping TGF-β1 codon 10 [rs1982073] and codon 25 [rs1800471] genetic polymorphisms. Enzyme-linked immunosorbent assay technique (ELISA) based on the sandwich principle was used for quantification of serum TGF-β1 level. Psoriasis Area and Severity Index (PASI) scoring was applied for determining the severity in psoriatic patients and classified accordingly to mild (PASI<7), moderate (PASI 7-12), severe (PASI>12) groups., Results: Statistically significant difference was found in TGF-β1 gene polymorphism between psoriatic patients and control group at codon 10 (T869C) polymorphism (p=0.021) and codon 25 (G915C) polymorphism (p=0.040). No significant association was detected with the mean serum TGF-β1 level, severity of the disease, disease onset, gender, history of psoriatic arthritis, and smoking in both codons. Significant lower mean serum TGF-β1 level was found among psoriatic group (192.17 ± 531.12 ng/L) compared with controls (565.89 ± 1372.30 ng/L) (p = 0.018). Relation of mean serum TGF-β1 level with the onset of the disease was statistically significant (p = 0.004), early-onset disease group was lower (105.92 ± 68.02 ng/L) compared with the late-onset disease group (450.92 ±1027.79 ng/L). The mean serum TGF-β1 level showed no significant differences with the severity of psoriasis, gender, history of psoriatic arthritis, and smoking., Conclusion: Iraqi population showed a significant association between TGF-β1 gene polymorphism at codon 10 and 25 were with psoriasis susceptibility, and a significantly lower mean serum TGF-β1 level was detected in psoriatic patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ahmed et al.)

Background: Vitiligo is a chronic acquired pigmentary disorder of the skin; it results from immunological distruction of functioning melanocytes. The cytokine TNF-α plays a central role in the initiation of melanocyte apoptosis in vitiligo. Single nucleotide polymorphism (SNP) in the promoter region of the gene coding for serum TNF-α may affect its production., Objective: The aim of this study is to assess serum TNF-α as a risk factor for generalized vitiligo among Iraqi patients and to rule out that polymorphism at the -308 position affects serum TNF-α., Materials and Methods: This case-control study was conducted at Sulaymaniyah Dermatology Teaching Center (SDTC), Iraq. Serum concentration of TNF-α was measured using enzyme linked immunosorbent assay (ELISA) technique in 80 patients with generalized vitiligo and 40 clinically healthy controls. The amplification refractory mutation system polymerase chain reaction (ARMS-PCR) technique was used for detection of TNF -308G/A gene polymorphism. TNF-α level correlated with TNF- 308G/A gene polymorphism. Serum concentration and TNF -308G/A gene polymorphism have been analyzed in correlation with demographic features and clinical characteristics of patients with generalized vitiligo., Results: Statistically significant elevation of serum TNF-α seen in patients compared to a control group ( p -value 0.01). Significantly higher TNF-α level ( p -value 0.01) found among patients with active generalized vitiligo. Elevated serum levels of TNF-α were significantly associated with both TNFA1 (TNF -308G ) allele ( p- value 0.04) and TNFA2 (TNF -308 A) allele ( p -value 0.03). TNF-α -308GA polymorphism was not affected by demographic features and clinical characteristics of patients with generalized vitiligo., Conclusion: TNF-α in the serum is a risk factor for generalized vitiligo among Iraqi patients. Patients with active vitiligo have a higher serum TNF-α level. No difference was found between serum level of TNF-α with TNF-α polymorphism at position -308 (TNF -308 ). This involves substituting G allele for the A allele., Competing Interests: The authors state that they have no conflicts of interest for this work., (© 2020 Ahmed et al.)

Copeptin is a precursor for arginine vasopressin which is usually elevated in acute stress and cardiac emergencies. Bisphenol A (BPA) is an ideal plasticizing factor used in manufacturing of plastics and epoxy resins. To evaluate the cardio toxicity of bisphenol A and to assess copeptin as a cardio toxic diagnostic and prognostic biomarker in Wistar rats. Sixty Wistar rats were classified into three groups: group I, naive group received regular diet and water; group II, vehicle group administered corn oil; and group III, each rat received BPA daily with (30 mg/kg/day S.C). After 4 weeks, blood samples were collected for estimating serum copeptin levels. Then, the hearts were subjected to histological, immunohistochemical, and electron microscopic examination. Cell suspensions from the hearts were examined to determine the extent of DNA damage by comet assay. Bisphenol A induced a significant increase in mean values of serum copeptin level, histopathological changes in the form of dilated congested blood vessels and extensive collagen fiber deposition in the myocardium. Ultrastructurally, disturbed indented nuclei, focal lysis of myofibrils, normal cross striations loss, mitochondrial swelling, and intercalated disks distortion were noticed. Immunohistochemical study showed a significant increase in TLR2 immunoreactions in the myocytes of BPA administered rats. In addition, comet assay showed that bisphenol A exposure produced DNA damage in cardiac cells. We concluded that bisphenol A has deleterious effects on cardiac tissues mean, while copeptin is a good diagnostic and prognostic biomarker.

The rational of the current study was to assess whether Tribulus terrestris extract (TTE) could alleviate long-term copper (Cu) overload-induced testicular dysfunction compared to enalapril and losartan. Rats were administered either vehicle (control group, n = 10) or copper sulfate pentahydrate (CuSO 4 ·5H 2 O, 200 mg/kg, p.o) for 90 days (n = 40). Cu-treated rats were randomized into four equal groups. One group was left untreated (Cu group) while the remaining three groups were daily co-treated with one of the following treatments along with CuSO4: TTE (10 mg/kg, p.o); enalapril (30 mg/kg, p.o); losartan (10 mg/kg, p.o). Excess Cu intake resulted in Cu overload coupled with a significant elevation in systolic blood pressure and serum angiotensin II levels along with a reduction in serum nitric oxide level. All concomitant treatments led to an alleviation of such deleterious effects. However, only losartan failed to ameliorate angiotensin II elevation. Additionally, all treatments protected the testes against Cu-overload-elicited zinc depletion and oxidative stress. Regarding reproductive function, the relative weights of testes, serum levels of testosterone and luteinizing hormone; the expression of steroidogenic genes; the protein levels of angiotensin II type 1 receptor and angiotensin converting enzyme 1, in addition to its activity, they were significantly reduced. Amongst all treatments, only TTE and E were able to revert these reproductive changes. In conclusion TTE and E were able to protect against Cu overload-induced impairment of testicular steroidogenesis. Thus, they might be considered as prophylactic drugs of choice against hypertension and testicular dysfunction to ameliorate Cu overload risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A recent outbreak of ischaemic teat necrosis (ITN) on mainland UK has resulted in large economic losses for dairy farmers. Typical cases start as an area of dry, thickened and encrusted skin on the medial aspect of the base of the teat, where the teat joins the udder, often with a fetid odour. The erosion spreads down the teat, often causing intense irritation, which in turn leads to more severely affected animals removing the entire teat. Due to the severity of ITN and the substantial economic costs to the industry, analyses were undertaken to ascertain if an infectious agent might be involved in the pathology. The study has considered a role for digital dermatitis (DD) treponemes in the aetiopathogenesis of ITN because, as well as being the prime bacteria associated with infectious lameness, they have been associated with a number of emerging skin diseases of cattle, including udder lesions. A high association between presence of DD-associated treponemes and incidence of ITN (19/22), compared with absence in the control population is reported. Furthermore, sequencing of the 16S rRNA gene of treponeme isolates supports the hypothesis that the identified treponemes are similar or identical to those isolated from classical foot DD lesions in cattle (and sheep). Further studies are required to allow effective targeted prevention measures and/or treatments to be developed., (British Veterinary Association.)

Toxoplama gondii (Apicomplexa: Coccidia), an obligatory intracellular parasite with a unique capacity to invade virtually all nucleated cell type from warm-blooded vertebrate hosts. Despite the efficiency with which Toxoplasma enters its host cell, it remains unresolved if invasion occurs by direct penetration of the parasite or through phagocytosis. In the present work, electron microscopic study was designed to examine the entry process of Toxoplasma (RH strain) into macrophages and non phagocytic-host cells (Hela cells) and to observe the ultrastructure changes associated with intracellular parasitism. The results showed that both active invasion and phagocytosis were occurred and revealed that invasion is an ordered process that initiates with binding of the parasite at its apical end followed by tight-fitting invagination of the host cell membrane and a prominent constriction in the parasite at the site of penetration. The process ended by the professional parasitophorous vacuole that is distinct at the outset from those formed by phagocytosis in which once Toxoplasma triggered, phagocytic uptake can proceed by capture of the parasite within a loose fitting vacuole formed by localized membrane ruffling. The cytopathic effects of the parasite on macrophages and Hela cells were demonstrated within 5-15 h post-inoculation in the form of degenerative mitochondria, swelling Golgi apparatus and widening of endoplasmic reticulum indicating intracellular oedema. These changes were exaggerated and several cells were found dead after 48-72 h.

This article is a review of the causative factors and pharmacologic treatments of diarrhea. This information was incorporated into a Diarrhea Assessment and Treatment Tool (DATT) to guide clinicians on comprehensive diarrhea assessment and current treatment recommendations. The tool was utilized at a university-affiliated oncology institution by a clinical nurse specialist on 26 patients as a performance improvement project. Ease of use and efficacy of DATT were tested. Eighty-one percent of patients were assessed using DATT in 30 minutes or less. Seventy-nine percent of the 57 identified diarrhea classifications were not being treated upon initial assessment. Diarrhea control was achieved in 73% of the patients within 7 days or fewer when DATT was utilized. The premise of diarrhea management is that if all the causative factors are not treated, diarrhea will persist. The conclusions are that this tool will aid the clinician in a comprehensive assessment of diarrhea and provide a systematic approach to diarrhea treatment. The need for research on best practice for management of the various causative factors of diarrhea is needed.

The infusion of a low dose of endotoxin into healthy subjects triggers a complex inflammatory response but the intricacies of which, despite extensive research, are still being unraveled. Nine healthy male volunteers received a dose of 30 Units endotoxin/kg bodyweight as an intravenous bolus. Following endotoxin infusion the concentration of TNF-alpha in their serum rapidly increased within 30 min, peaked after 1-2 h and returned to baseline by 4 h. This corresponded to a similarly rapid increase in anti-inflammatory soluble TNF receptor (sTNFR) levels, which remained elevated for up to 48 h. Increased levels of other cytokines were measured, including IL-6, IL-8, G-CSF, IL-1ra and IL-10. However, these cytokines lagged behind that of TNF-alpha and remained elevated for up to 8 h. Endotoxin injection resulted in complex changes in HLA-DR expression, a marker of monocyte activation state. Initially, following a lag of 2-4 h, HLA-DR expression decreased with a nadir at 8 h, followed by an increase in expression above baseline at 22 h. HLA-DR levels returned to baseline 48 h post-endotoxin challenge. This was in contrast to endotoxin-induced changes in white blood cell (WBC) numbers, which dropped rapidly (at 2-3 h) while HLA-DR levels were stable and then peaked during the nadir in HLA-DR expression (8 h). Furthermore, endotoxin injection caused activation of both fibrinolytic and coagulation pathways. Thus, endotoxin infusion results in complex changes in HLA-DR expression, production of pro- and anti-inflammatory cytokines and activation of coagulation.

Aims: To investigate the tolerability, safety and pharmacokinetics of S-3304 in healthy volunteers treated with high doses of S-3304 for 28 days., Methods: Thirty-two healthy volunteers were recruited. Four male and four female subjects were allocated to one of four doses (800 mg, 1600 mg, 2400 mg and 3200 mg). At each dose six volunteers took active medication and two volunteers took placebo in a double-blind fashion. Volunteers took a single dose on days 1 and 28 for pharmacokinetic purposes, and took twice daily doses from day 3-27. The pharmacokinetics of S-3304 and its hydroxy metabolites were evaluated. Tolerance was based on subjective adverse events, clinical examination, vital signs, ECG and laboratory tests including haematology and biochemistry profiles using CTC grading., Results: Doses up to 2400 mg twice daily were generally well tolerated. At 3200 mg twice daily, five volunteers including one randomized to placebo were withdrawn from treatment mainly due to alanine aminotransferase (ALT) elevation. C(max) of S-3304 on day 1, whose geometric mean and 95% confidence interval were 66.3 microg ml(-1) (48.8, 90.0) for 800 mg, 82.6 microg ml(-1) (69.3, 98.6) for 1600 mg, 89.5 microg ml(-1) (79.5, 100.7) for 2400 mg, and 110.5 microg ml(-1) (88.9, 137.7) for 3200 mg, respectively, was correlated with the log-transformed peak ALT (P < 0.0001 for male and P = 0.048 for female volunteers)., Conclusions: In healthy volunteers the maximum tolerated dose of S-3304 was 2400 mg twice daily. ALT elevation was the most frequent dose-limiting factor and was correlated with C(max) on day 1.

Plasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of REVASC before, during and after a DDAVP infusion were investigated. Twelve healthy volunteers were given an intravenous bolus dose followed by a constant rate four-hour infusion of REVASC. Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three hours respectively after the start of the REVASC infusion. Plasma REVASC concentrations were not affected by either the saline or DDAVP infusion. REVASC infusion produced an increase in APTT which plateaued between 0.5 and 3 hours. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the REVASC infusion continued. There were no serious adverse events or bleeding episodes throughout the study. In conclusion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of REVASC and partially reverses the REVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by REVASC.