Oral post-treatment supplementation with a combination of glutamine, citrulline, and antioxidant vitamins additively mitigates jejunal damage, oxidative stress, and inflammation in rats with intestinal ischemia and reperfusion.

INTRODUCTION: Intestinal ischemia and reperfusion (IIR) injury is closely associated with oxidative stress. Evidence shows that oral supplementation with glutamine and citrulline alleviates IIR-induced jejunal damage. We investigated the effects of a combination of glutamine, citrulline, and antioxidant vitamins on IIR-induced jejunal damage, oxidative stress, and inflammation. METHOD: Male Wistar rats that underwent 60 min of superior mesenteric artery occlusion were orally administered glutamine plus citrulline (GC), vitamin C plus E (CE), or a combination of GC and CE 15 min before and 3, 9, and 21 h after reperfusion. Healthy rats without IIR were used as controls. RESULTS: After reperfusion for 24 h, rats with IIR showed lower levels of red blood cells, hemoglobin, serum glucose, and jejunal DNA and increased white blood cell counts compared to controls (1-way ANOVA with the least significant difference, P < 0.05). The IIR-induced decrease in serum albumin and increase in plasma interleukin-6 and jejunal thiobarbituric acid-reactive substances (TBARS) were significantly reversed by GC and/or CE. The results of the 2-way ANOVA indicated that GC was the main factor that increased jejunal villus height and muscularis DNA, and CE was the main factor that increased jejunal muscularis protein and decreased jejunal proinflammatory cytokine levels and myeloperoxidase activity. In addition, GC and CE are the main factors that decrease plasma proinflammatory cytokine levels and the jejunal apoptotic index. CONCLUSION: Oral post-treatment supplementation with glutamine and citrulline, combined with vitamins C and E, may alleviate IIR-induced oxidative stress, inflammation, and jejunal damage.

DIONYSIUS trial: "Does increasing oxygen nurture your symptomatic ischaemic ulcer sufficiently?" Study protocol for an international multicentre randomised trial.

INTRODUCTION: Diabetic foot ulcers (DFUs) are a major complication of diabetes and often associated with peripheral arterial occlusive disease. Current available evidence shows hyperbaric oxygen therapy (HBOT) can reduce the risk of major amputation, but clinicians remain sceptical about the (cost-)effectiveness and feasibility of HBOT for ischaemic DFUs in clinical practice. Therefore, vascular surgeons and HBOT physicians worldwide feel a strong need for a sufficiently powered clinical trial to determine whether and how many HBOT sessions may be a (cost-)effective adjunctive treatment to ischaemic DFUs. METHODS: An international, multicentre, multi-arm multi-stage design is chosen to conduct an efficient randomised clinical trial. Patients will be randomised to receive standard care (wound treatment and surgical interventions following international guidelines) with either 0, 20, 30 or at least 40 sessions of HBOT. These sessions will comprise 90-120 min of HBOT at a pressure of 2.2-2.5 atmospheres absolute according to international standards. Based on a planned interim analysis, the best performing study arm(s) will continue. Primary end point is major amputation (ie, above ankle) rate after 12 months. Secondary end points are amputation-free survival, wound healing, health-related quality of life and cost-effectiveness. ETHICS AND DISSEMINATION: All patients enrolled in this trial will receive maximum vascular, endovascular or conservative treatment and local wound care according to best practice and (inter)national guidelines. HBOT therapy is added to the standard treatment and is regarded as a low-risk to moderate-risk therapy. The study is approved by the medical ethics committee of the Amsterdam University Medical Centers, location University of Amsterdam. TRIAL REGISTRATION NUMBER: 2020-000449-15, NL9152, NCT05804097.

Skeletal Muscle Bioenergetics in Critical Limb Ischemia and Diabetes.

INTRODUCTION: Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus (T2DM) is a major risk factor for PAD development and progression to CLI and may also independently be related to mitochondrial dysfunction. We set out to determine the effect of T2DM in the relationship between CLI and muscle mitochondrial respiratory capacity and coupling control. METHODS: We studied CLI patients undergoing revascularization procedures or amputation, and non-CLI patients with or without T2DM of similar age. Mitochondrial respiratory capacity and function were determined in lower limb permeabilized myofibers by high-resolution respirometry. RESULTS: Fourteen CLI patients (65 ± 10y) were stratified into CLI patients with (n = 8) or without (n = 6) T2DM and were compared to non-CLI patients with (n = 18; 69 ± 5y) or without (n = 19; 71 ± 6y) T2DM. Presence of CLI but not T2DM had a marked impact on all mitochondrial respiratory states in skeletal muscle, adjusted for the effects of sex. Leak respiration (State 2, P < 0.025 and State 4o, P < 0.01), phosphorylating respiration (P < 0.001), and maximal respiration in the uncoupled state (P < 0.001), were all suppressed in CLI patients, independent of T2DM. T2DM had no significant effect on mitochondrial respiratory capacity and function in adults without CLI. CONCLUSIONS: Skeletal muscle mitochondrial respiratory capacity was blunted by ∼35% in patients with CLI. T2DM was not associated with muscle oxidative capacity and did not moderate the relationship between muscle mitochondrial respiratory capacity and CLI.

Deep nuclei injury distribution in isolated "basal ganglia-thalamus" (BGT) versus combined "BGT and watershed" patterns of hypoxic-ischaemic injury (HII) in children with cerebral palsy.

AIM: To compare frequency and distribution of deep nuclei involvement in isolated basal ganglia and ventrolateral thalamus (BGT) versus combined BGT and watershed (BGT-WS) hypoxic-ischaemic injury (HII). MATERIALS AND METHODS: A retrospective review was undertaken of the magnetic resonance imaging (MRI) reports of children (0-18 years) with isolated BGT or combined BGT-WS HII. The location and extent of deep nuclear injuries were compared between groups using Fisher's exact test. RESULTS: Of 762 MRI reports, 435 (57%) had isolated BGT and 327 (43%) combined BGT-WS. Isolated BGT showed basal ganglia involvement in 85.1% (n=370) versus 49.8% (n=163) for combined BGT-WS (p<0.01). Sole putamen lesions were more common in isolated BGT (70.3%; 306) versus combined (19.3%; 63; p<0.01). Thalamic involvement was similar between isolated BGT (93.8%; 408) and combined BGT-WS (96.9%; 317; p>0.05). Sole ventrolateral nucleus involvement was more common in isolated BGT (66.6%; 291) while sole pulvinar lesions (25.1%; 82) and whole thalamus lesions (41.6%; 136) were more common in combined BGT-WS (p<0.01). Putamen and ventrolateral nucleus was the most frequent BGT lesion combination in isolated BGT (55.4%) but not in combined BGT-WS (8.6%; p<0.01). CONCLUSION: Variations in the frequency of deep nuclear lesions between groups may reflect different underlying pathogenetic mechanisms. Therefore, combined BGT-WS patterns may not necessarily indicate a superimposed profound on partial prolonged HII, as other causes such as neonatal hypoglycaemia may cause these.

Impact of Serum Zinc Level and Oral Zinc Supplementation on Clinical Outcomes in Patients Undergoing Infrainguinal Bypass for Chronic Limb-Threatening Ischemia.

BACKGROUND: Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery.Methods and Results: This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 µg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). CONCLUSIONS: The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

TGF-ß loaded exosome enhances ischemic wound healing in vitro and in vivo.

Rationale: With over seven million infections and $25 billion treatment cost, chronic ischemic wounds are one of the most serious complications in the United States. The controlled release of bioactive factor enriched exosome from finbrin gel was a promising strategy to promote wound healing. Methods: To address this unsolved problem, we developed clinical-grade platelets exosome product (PEP), which was incorporate with injectable surgical fibrin sealant (TISSEEL), to promote chronic wound healing and complete skin regeneration. The PEP characterization stimulated cellular activities and in vivo rabbit ischemic wound healing capacity of TISSEEL-PEP were performed and analyzed. Results: PEP, enriched with transforming growth factor beta (TGF-ß), possessed exosomal characteristics including exosome size, morphology, and typical markers including CD63, CD9, and ALG-2-interacting protein X (Alix). In vitro, PEP significantly promoted cell proliferation, migration, tube formation, as well as skin organoid formation. Topical treatment of ischemic wounds with TISSEEL-PEP promoted full-thickness healing with the reacquisition of hair follicles and sebaceous glands. Superior to untreated and TISSEEL-only treated controls, TISSEEL-PEP drove cutaneous healing associated with collagen synthesis and restoration of dermal architecture. Furthermore, PEP promoted epithelial and vascular cell activity enhancing angiogenesis to restore blood flow and mature skin function. Transcriptome deconvolution of TISSEEL-PEP versus TISSEEL-only treated wounds prioritized regenerative pathways encompassing neovascularization, matrix remodeling and tissue growth. Conclusion: This room-temperature stable, lyophilized exosome product is thus capable of delivering a bioactive transforming growth factor beta to drive regenerative events.

AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice.

Peripheral arterial disease occurs more frequently and has a worse prognosis in patients with chronic kidney disease (CKD). The receptor for advanced glycation end products (RAGE) is involved in multiple aspects of uremia-associated vasculopathy. Previous data suggest that the RAGE pathway may promote soluble fms-like tyrosine kinase 1 (sFlt1) production, an anti-angiogenic molecule. Thus, we tested the hypothesis that the deletion of AgeR would decrease sFlt1 production and improve post-ischemic revascularization in uremic condition. We used a well-established CKD model (5/6 nephrectomy) in WT and AgeR-/- C57/Bl6 mice. Hindlimb ischemia was induced by femoral artery ligation. Revascularization was evaluated by complementary approaches: ischemic limb retraction, LASCA imagery, and capillary density. The production of sFlt1 was assessed at both RNA and protein levels. After hindlimb ischemia, uremic mice showed slower functional recovery (p < 0.01), decreased reperfusion (p < 0.01), lower capillary density (p = 0.02), and increased circulating sFlt1 levels (p = 0.03). AgeR deletion restored post-ischemic angiogenesis and was protective from sFlt1 increase in uremic mice. These findings show the main role of RAGE in post-ischemic angiogenesis impairment associated with CKD. RAGE may represent a key target for building new therapeutic approaches to improve the outcome of CKD patients with PAD.

[Clinical observation of the therapeutic effect on posterior circulation ischemic vertigo treated with "xiao xingnao kaiqiao" acupuncture].

OBJECTIVE: To observe the short-term and long-term clinical effect on posterior circulation ischemic vertigo treated with "xiao xingnao kaiqiao" acupuncture (minor regaining consciousness and opening orifice) and explore its effect mechanism. METHODS: Ninety patients with posterior circulation ischemic vertigo were randomly divided into a treatment group and a control group, 45 cases in each group. The patients of the two groups were all treated on the base of neurological medicine. In the control group, Flunarizine Hydrochloride was prescribed for oral administration (5 mg, once daily, for 21 days totally). In the treatment group, acupuncture of "xiao xingnao kaiqiao" was provided at Yintang (EX-HN3), bilateral Neiguan (PC6), bilateral Sanyinjiao (SP6), Baihui (GV20), bilateral Fengchi (GB20), bilateral Wangu (GB12) and bilateral Tianzhu (BL10). The needles were retained for 30 min, once daily for 21 days totally. The changes in vertigo score of traditional Chinese medicine (TCM) were observed, and the changes in the mean blood velocity (Vm) of the left vertebral artery (LVA), the right vertebral artery (RVA) and the basilar artery (BA) as well as the vascular pulsatility index (PI) were monitored and determined by transcranial Doppler (TCD). Additionally, the recurrence rate was followed up after 3 months to evaluate the long-term clinical effects. RESULTS: After treatment, the total effective rate of the treatment group was 91.11% (41/45) and 75.56% (34/45) in the control group. The total effective rate in the treatment group was higher than that in the control group (P<0.05). Compared with their own pre-treatment, the vertigo scores of TCM were reduced in either the treatment group or the control group after treatment (P<0.05) and the score in the treatment group was lower than that in the control group (P<0.05). Compared with their own pre-treatment, Vm and PI were all improved after treatment in either group (P < 0.05). After treatment, the improvements in Vm and PI of LVA、RVA and BA in the treatment group were better than those in the control group (P<0.05). In the follow-up after 3 months, the recurrence rate was 19.51% (8/41) in the treatment group and was 50.00% (17/34) in the control group. The recurrence rate in the treatment group was lower than that in the control group (P<0.05). CONCLUSION: "Xiao xingnao kaiqiao" acupuncture obviously relieves the clinical symptoms of posterior circulation ischemic vertigo. The mechanism of acupuncture is potentially related with its effects in improving Vm and PI of LVA,RVA and BA, as well as improving blood supply of brain tissue.

Maternal alcoholism and neonatal hypoxia-ischemia: Neuroprotection by stilbenoid polyphenols.

The impact of maternal nutrition on neurodevelopment and neonatal neuroprotection is a research topic with increasing interest. Maternal diet can also have deleterious effects on fetal brain development. Fetal exposure to alcohol is responsible for poor neonatal global development, and may increase brain vulnerability to hypoxic-ischemic encephalopathy, one of the major causes of acute mortality and chronic neurological disability in newborns. Despite frequent prevention campaigns, about 10% of women in the general population drinks alcohol during pregnancy and breastfeeding. This study was inspired by this alarming fact. Its aim was to evaluate the beneficial effects of maternal supplementation with two polyphenols during pregnancy and breastfeeding, on hypoxic-ischemic neonate rat brain damages, sensorimotor and cognitive impairments, in a context of moderate maternal alcoholism. Both stilbenoid polyphenols, trans-resveratrol (RSV - 0.15 mg/kg/day), and its hydroxylated analog, trans-piceatannol (PIC - 0.15 mg/kg/day), were administered in the drinking water, containing or not alcohol (0.5 g/kg/day). In a 7-day post-natal rat model of hypoxia-ischemia (HI), our data showed that moderate maternal alcoholism does not increase brain lesion volumes measured by MRI but leads to higher motor impairments. RSV supplementation could not reverse the deleterious effects of HI coupled with maternal alcoholism. However, PIC supplementation led to a recovery of all sensorimotor and cognitive functions. This neuroprotection was obtained with a dose of PIC corresponding to the consumption of a single passion fruit per day for a pregnant woman.

[Analysis on transcriptionomic characteristics of Naoxintong Capsules in prevention of post-ischemic inflammation based on RNA-Seq technology].

In this research, high-throughput sequencing was used to investigate the mechanism of Naoxintong Capsules(NXTC) in prevention of post-ischemic inflammation. First, microglia BV-2 inflammatory model was induced by 1.0 µg·mL~(-1) LPS to investigate the effect of intestinal absorption solution of NXTC(NXTCIA) at different concentrations(62.5, 31.25, 15.63, 7.81 µg·mL~(-1)) on LPS-induced BV-2 inflammatory factors in microglia. Then, an RNA-Seq high-throughput sequencing method was performed to identify the differentially expressed mRNAs in microglia BV-2 after pre-treatment with NXTC. GO and KEGG enrichment analysis was used to screen the potential biological processes and related signaling pathways of NXTC in inhibiting inflammation. The results showed that four NXTCIA concentrations could significantly inhibit the release of LPS-induced inflammatory mediators in BV-2 in a dose-dependent manner. Furthermore, high-throughput sequencing results showed that 392 mRNA transcripts were reversed following pre-treatment with NXTC. GO enrichment analysis showed that the transcripts reversed by NXTC were mainly involved in Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway. Taken together, our findings showed that NXTC treatment could provide protective effects against inflammatory response and the mechanism might be related to the regulation of Toll-like receptor signaling pathway, chemokine signaling pathway, and TNF signaling pathway.

[Effects of fast-twisting long-retaining acupuncture therapy on apoptosis and expression of related proteins in vestibular nucleus in rats with vertigo induced by posterior circulation ischemia].

OBJECTIVE: To observe the effects of fast-twisting long-retaining (FTLR) acupuncture therapy on apoptosis of vestibular nucleus and expression of Caspase-3, Bcl-2 and Bax in rats with vertigo induced by posterior circulation ischemia. METHODS: A total of 70 healthy SD rats were randomly divided into a sham operation group, a model group, a medication group, a regular acupuncture group and a FTLR acupuncture group, 14 rats in each group. The rats in the model group, medication group, regular acupuncture group and FTLR acupuncture group were intervented with surgical ligation of the right common carotid artery (CCA) and the right subclavian artery (SCA) to establish the model of vertigo induced by posterior circulation ischemia; in the sham operation group, the right CCA and the right SCA were separated without ligation. The rats in the medication group were treated with gavage of flunarizine hydrochloride suspension (10 mL/kg). "Baihui" (GV 20), "Shuaigu" (GB 8) and "Fengchi" (GB 20) were selected in the two acupuncture groups. The rats in the regular acupuncture group were treated with routine acupuncture and the needles were retained for 30 min, while the rats in the FTLR acupuncture group were treated with quick twist (200-300 times/min) for 1 min and the needles were retained for 60 min. The rats in the sham operation group and the model group received no intervention. All the intervention was provided once a day for 10 days. The decline rate of local blood flow in vestibular nucleus was observed; the apoptosis of vestibular nucleus was observed by TUNEL method; the expression of Caspase-3, Bcl-2 and Bax proteins were detected by immunohistochemistry. RESULTS: Compared with the sham operation group, the decline rate of local blood flow in the right vestibular nucleus was significantly increased in the model group (P<0.01), and the apoptosis index (AI) of vestibular nucleus was significantly increased (P<0.01). Compared with the model group, the decline rates of local blood flow in the right vestibular nucleus in the two acupuncture groups and medication group were significantly reduced (P<0.01), and the AIs of vestibular nucleus cells were significantly reduced (P<0.01). The decline rate of local blood flow in the right vestibular nucleus in the FTLR acupuncture group was lower than those in the medication group and the regular acupuncture group (P<0.01, P<0.05), and the AI of vestibular nucleus was lower than those in the regular acupuncture group and the medication group (P<0.05). Compared with the sham operation group, the expression of Bcl-2 in the vestibular nucleus was significantly decreased in the model group (P<0.01), and the expressions of Bax and Caspase-3 were significantly increased (P<0.01). Compared with the model group, the expressions of Bcl-2 in the vestibular nucleus were significantly increased in the two acupuncture groups and medication group (P<0.01), and the expressions of Bax and Caspase-3 were significantly reduced (P<0.01). The expression of Bcl-2 in the vestibular nucleus in the FTLR acupuncture group was higher than those in the regular acupuncture group and the medication group (P<0.05), and the expressions of Bax and Caspase-3 were lower than those in the regular acupuncture group and the medication group (P<0.05). CONCLUSION: The FTLR acupuncture therapy could effectively inhibit the apoptosis of vestibular nucleus in rats with vertigo induced by posterior circulation ischemia, and its mechanism may be related to improving the blood supply of vestibular nucleus and regulating the expressions of Caspase-3, Bcl-2 and Bax proteins.

Combined therapy of photobiomodulation and adipose-derived stem cells synergistically improve healing in an ischemic, infected and delayed healing wound model in rats with type 1 diabetes mellitus.

OBJECTIVE: We assessed the therapeutic effects of photobiomodulation (PBM) and adipose-derived stem cell (ADS) treatments individually and together on the maturation step of repairing of a delayed healing wound model in rats with type 1 diabetes mellitus (DM1). RESEARCH DESIGN AND METHODS: We randomly assigned 24 rats with DM1 to four groups (n=6 per group). Group 1 was the control (placebo) group. In group 2, allograft human ADSs were transplanted. Group 3 was subjected to PBM (wavelength: 890 nm, peak power output: 80 W, pulse frequency: 80 Hz, pulsed duration: 180 ns, duration of exposure for each point: 200 s, power density: 0.001 W/cm2, energy density: 0.2 J/cm2) immediately after surgery, which continued for 6 days per week for 16 days. Group 4 received both the human ADS and PBM. In addition, we inflicted an ischemic, delayed healing, and infected wound simulation in all of the rats. The wounds were infected with methicillin-resistant Staphylococcus aureus (MRSA). RESULTS: All three treatment regimens significantly decreased the amount of microbial flora, significantly increased wound strength and significantly modulated inflammatory response and significantly increased angiogenesis on day 16. Microbiological analysis showed that PBM+ADS was significantly better than PBM and ADS alone. In terms of wound closure rate and angiogenesis, PBM+ADS was significantly better than the PBM, ADS and control groups. CONCLUSIONS: Combination therapy of PBM+ADS is more effective that either PBM or ADS in stimulating skin injury repair, and modulating inflammatory response in an MRSA-infected wound model of rats with DM1.

Effects of dietary glutamine supplementation on immune cell polarization and muscle regeneration in diabetic mice with limb ischemia.

PURPOSE: Diabetes is a chronic inflammatory disorder resulting in endothelial dysfunction which contributes to peripheral arterial disease and limb ischemia. Leukocytes play critical roles in vascular and tissue remodelling after ischemia. This study investigated the effects of dietary glutamine (GLN) supplementation on immune cell polarization in diabetic mice subjected to limb ischemia. METHODS: Diabetes was induced by an intraperitoneal injection of streptozotocin for 5 consecutive days in C57BL/6J mice. Diabetic mice were fed the AIN-93 diet or an AIN-93 diet in which a part of the casein was replaced by GLN. After 3 weeks of the dietary intervention, mice were subjected to unilateral femoral artery ligation to induce limb ischemia. RESULTS: GLN supplementation enhanced the proportion of anti-inflammatory monocytes and regulatory T cells in the blood. Expression of C-C motif chemokine receptor 5 by activated CD4+ T cells was promoted and prolonged in the GLN-supplemented group. GLN downregulated the percentage of M1 macrophages in muscle tissues which was correlated with lower levels of C-C motif chemokine ligand 2 in plasma. The muscle M1/M2 ratio was also reduced in the GLN group. Gene expression of interleukin-6 was suppressed by GLN supplementation, while expression levels of the peroxisome proliferator-activated receptor γ and myogenic differentiation 1 genes were elevated in post-ischemic muscles. Histological findings also indicated that muscle regeneration was accelerated in the GLN group. CONCLUSIONS: GLN supplementation in diabetic mice may exert more-balanced polarization of CD4+ T cells, monocytes, and macrophages, thus attenuating inflammatory responses and contributing to muscle regeneration after limb ischemia.

Hyperbaric oxygen therapy for nonischemic diabetic ulcers: A systematic review.

Diabetic foot ulcers are a common complication of diabetes, which affects 25% of patients and may ultimately lead to amputation of affected limbs. Research suggests hyperbaric oxygen therapy improves healing of these ulcers. However, this has not been reflected in previous reviews, possibly because they did not differentiate between patients with and without peripheral arterial occlusive disease. Therefore, we performed a systematic review of published literature in the MEDLINE, Embase, and Cochrane CENTRAL databases on nonischemic diabetic foot ulcers with outcome measures including complete ulcer healing, amputation rate (major and minor), and mortality. Seven studies were included, of which two were randomized clinical trials. Two studies found no difference in major amputation rate, whereas one large retrospective study found 2% more major amputations in the hyperbaric oxygen group. However, this study did not correct for baseline differences. Two studies showed no significant difference in minor amputation rate. Five studies reporting on complete wound healing showed no significant differences. In conclusion, the current evidence suggests that hyperbaric oxygen therapy does not accelerate wound healing and does not prevent major or minor amputations in patients with a diabetic foot ulcer without peripheral arterial occlusive disease. Based on the available evidence, routine clinical use of this therapy cannot be recommended. However, the available research for this specific subgroup of patients is scarce, and physicians should counsel patients on expected risks and benefits. Additional research, focusing especially on patient selection criteria, is needed to better identify patients that might profit from this therapy modality.

Falla intestinal. Artículo de revisión / Intestinal failure Review article

La falla intestinal (FI) se define como la disminución de la función del intestino por debajo de lo mínimo necesario para la absorción de los macronutrientes y / o agua y electrolitos, de tal manera que se requiere de la suplementación intravenosa (SIV) para mantener la salud y el crecimiento. Desde el punto de vista funcional se clasifica en tres tipos. FI tipo I: condición aguda, de corto duración y generalmente auto limitada, FI tipo II: estado agudo prolongado, a menudo en pacientes metabólicamente inestables, que requieren cuidado multidisciplinario y SIV durante períodos de una semana o meses, acompañada de complicaciones sépticas, metabólicas y nutricionales y FI tipo III: condición crónica, en pacientes metabólicamente estables, que requieren SIV durante meses o años. Su manejo requiere de terapia nutricional y en casos seleccionados cirugía autóloga de reconstrucción(AU)

Intestinal failure (FI) is defined as the decrease in intestinal function below the minimum necessary for the absorption of macronutrients and / or water and electrolytes, in such a way that intravenous supplementation (IVS) is required to maintain health and growth. From a functional point of view, it is classified into three types. FI type I: acute condition, of short duration and generally self-limited, FI type II: prolonged acute state, often in metabolically unstable patients, requiring multidisciplinary care and SIV for periods of a week or months, accompanied by septic, metabolic and nutrition and FI type III: chronic condition, in metabolically stable patients, who require SIV for months or years. Its management requires nutritional therapy and in selected cases autologous reconstruction surgery(AU)

Effects of Justicia acuminatissima, or Amazonian Sara Tudo, on ischemic acute kidney injury: an experimental study. / Efeito da Justicia acuminatissima, Sara Tudo do Amazonas, na injúria renal aguda isquêmica: estudo experimental.

OBJECTIVE: To evaluate the effects of Justicia acuminatissima , or Amazonian Sara Tudo , on renal hemodynamics, oxidative profile, and renal histology in rats with ischemic acute kidney injury. METHOD: Preclinical assay with adult male Wistar rats, weighing from 250 g to 350 g, distributed into Sham, ischemia, and ischemia + Sara Tudo groups. Hemodynamic parameters, renal function, oxidative stress, and renal histology were evaluated. RESULTS: Pretreatment with Sara Tudo reduced the functional injury, which was shown by the increase in creatinine clearance and thiols; reduction of oxidative markers, renal vascular resistance, and tubulointerstitial injury in the renal tissue; and the significant improvement in renal blood flow. CONCLUSION: The renoprotection provided by Justicia acuminatissima , or Sara Tudo , in cases of ischemic acute kidney injury was characterized by a marked improvement in renal function, reducing the oxidative injury, and impacting on renal histology positively.

Gross anterior segment ischaemia following vitreoretinal surgery for sickle-cell retinopathy.

We report the case of a 32-year-old Afrocaribbean man with known stage 3 proliferative sickle-cell retinopathy who presented with a mixed picture of tractional and rhegmatogenous macula off detachment. He underwent left primary 25 g vitrectomy with silicone oil, delamination and endolaser photocoagulation under a general anaesthetic. He, however, presented 48 hours postoperatively with gross anterior segment ischaemia. His pain and ocular signs settled over the course of a few days following administration of supplemental oxygen, oral steroids, analgesia and intravenous hydration. Examination showed resolution of his proptosis and orbital signs as well as anterior segment inflammation. He remains under follow-up.

Development of a contaminated ischemic porcine wound model and the evaluation of bromelain based enzymatic debridement.

OBJECTIVES: There are no well accepted animal models of chronic wounds, limiting advances in understanding and treatment of chronic ulcers. We developed a porcine wound model which combines multiple factors involved in chronic wounds to create a contaminated necrotic eschar and evaluated the debriding efficacy of a novel bromelain based enzymatic debriding agent (EscharEx). METHODS: Contaminated ischemic wounds were created on the flanks of domestic pigs by 'sandwiching' the skin between 2 'O' rings (1 placed on the surface of the skin and the other underneath the skin) for 24h prior to dermatomal excision of the necrotic eschar and its contamination with Staphylococcus aureus and Candida albicans. After confirming the development of infected eschars, additional animals were used to compare the effects of daily application of topical EscharEx or its hydrating vehicle on eschar debridement as a control. RESULTS: In all cases, application of the 'O' rings resulted in full thickness necrotic ecshars with invasive infections, which did not reepithelialize and sloughed off spontaneously within 14-21 days. All wounds reepithelialized within 28-42 days forming contracted scars. All EscharEx treated eschars were completely debrided within 7-9 days, while no debridement was evident in eschars treated with the control gel. CONCLUSIONS: Our model simulates the initial phase of chronic wounds characterized by a contaminated necrotic eschar allowing evaluation of wound debriding agents, and that a bromelain-based debriding agent completely debrides the contaminated necrotic eschars within one week in this model.

No effect of a pulsed magnetic field on induced ischemic muscle pain. A double-blind, randomized, placebo-controlled trial.

Empirical evidence supporting the effectiveness of pulsed (electro)magnetic field (PEMF) therapy on chronic and acute pain is equivocal. In the current randomized, double-blind, placebo-controlled experiment, impact of a commercially available whole-body PEMF mat on acute ischemic muscle pain induced in the forearm was studied with the participation of 70 healthy volunteers. The device emitted a pulsed magnetic field with a repetition frequency of 2.05Hz and a maximum flux density of 25.3µT (rms). The highest dB/dt was 48mT/s. No differences between the groups receiving actual and sham PEMF were found in terms of pain threshold, pain tolerance, heart rate, and perceived decrease of pain. However, participants' expectation concerning the effectiveness of the intervention improved pain tolerance and affected perceived change of pain. In conclusion, the used PEMF device had no specific effect on acute ischemic muscle pain, while the contribution of the placebo effect was considerable.