Split tendon transfers for the correction of spastic varus foot deformity: a case series study

<p>Abstract</p> <p>Background</p> <p>Overactivity of anterior and/or posterior tibial tendon may be a causative factor of spastic varus foot deformity. The prevalence of their dysfunction has been reported with not well defined results. Although gait analysis and dynamic electromyography provide useful information for the assessment of the patients, they are not available in every hospital. The purpose of the current study is to identify the causative muscle producing the deformity and apply the most suitable technique for its correction.</p> <p>Methods</p> <p>We retrospectively evaluated 48 consecutive ambulant patients (52 feet) with spastic paralysis due to cerebral palsy. The average age at the time of the operation was 12,4 yrs (9-18) and the mean follow-up 7,8 yrs (4-14). Eigtheen feet presented equinus hind foot deformity due to gastrocnemius and soleus shortening. According to the deformity, the feet were divided in two groups (Group I with forefoot and midfoot inversion and Group II with hindfoot varus). The deformities were flexible in all cases in both groups. Split anterior tibial tendon transfer (SPLATT) was performed in Group I (11 feet), while split posterior tibial tendon transfer (SPOTT) was performed in Group II (38 feet). In 3 feet both procedures were performed. Achilles tendon sliding lengthening (Hoke procedure) was done in 18 feet either preoperatively or concomitantly with the index procedure.</p> <p>Results</p> <p>The results in Group I, were rated according to Hoffer's clinical criteria as excellent in 8 feet and satisfactory in 3, while in Group II according to Kling's clinical criteria were rated as excellent in 20 feet, good in 14 and poor in 4. The feet with poor results presented residual varus deformity due to intraoperative technical errors.</p> <p>Conclusion</p> <p>Overactivity of the anterior tibial tendon produces inversion most prominent in the forefoot and midfoot and similarly overactivity of the posterior tibial tendon produces hindfoot varus. The deformity can be clinically unidentifiable in some cases when Achilles shortening co-exists producing foot equinus. By identifying the muscle causing the deformity and performing the appropriate technique, very satisfying results were achieved in the majority of our cases. In three feet both muscles contributed to a combined deformity and simultaneous SPLATT and SPOTT were considered necessary. For complex foot deformities where the component of cavus co-exists, supplementary procedures are required along with the index operation to obtain the best result.</p

A Cysteine Protease Is Critical for Babesia spp. Transmission in Haemaphysalis Ticks

Vector ticks possess a unique system that enables them to digest large amounts of host blood and to transmit various animal and human pathogens, suggesting the existence of evolutionally acquired proteolytic mechanisms. We report here the molecular and reverse genetic characterization of a multifunctional cysteine protease, longipain, from the babesial parasite vector tick Haemaphysalis longicornis. Longipain shares structural similarity with papain-family cysteine proteases obtained from invertebrates and vertebrates. Endogenous longipain was mainly expressed in the midgut epithelium and was specifically localized at lysosomal vacuoles and possibly released into the lumen. Its expression was up-regulated by host blood feeding. Enzymatic functional assays using in vitro and in vivo substrates revealed that longipain hydrolysis occurs over a broad range of pH and temperature. Haemoparasiticidal assays showed that longipain dose-dependently killed tick-borne Babesia parasites, and its babesiacidal effect occurred via specific adherence to the parasite membranes. Disruption of endogenous longipain by RNA interference revealed that longipain is involved in the digestion of the host blood meal. In addition, the knockdown ticks contained an increased number of parasites, suggesting that longipain exerts a killing effect against the midgut-stage Babesia parasites in ticks. Our results suggest that longipain is essential for tick survival, and may have a role in controlling the transmission of tick-transmittable Babesia parasites

Transcriptomic and functional analysis of the Anopheles gambiae salivary gland in relation to blood feeding

<p>Abstract</p> <p>Background</p> <p>The <it>Anopheles gambiae </it>salivary glands play a major role in malaria transmission and express a variety of bioactive components that facilitate blood-feeding by preventing platelet aggregation, blood clotting, vasodilatation, and inflammatory and other reactions at the probing site on the vertebrate host.</p> <p>Results</p> <p>We have performed a global transcriptome analysis of the <it>A. gambiae </it>salivary gland response to blood-feeding, to identify candidate genes that are involved in hematophagy. A total of 4,978 genes were found to be transcribed in this tissue. A comparison of salivary gland transcriptomes prior to and after blood-feeding identified 52 and 41 transcripts that were significantly up-regulated and down-regulated, respectively. Ten genes were further selected to assess their role in the blood-feeding process using RNAi-mediated gene silencing methodology. Depletion of the salivary gland genes encoding <it>D7L2</it>, <it>anophelin</it>, <it>peroxidase</it>, the <it>SG2 precursor</it>, and a <it>5'nucleotidase </it>gene significantly increased probing time of <it>A. gambiae </it>mosquitoes and thereby their capacity to blood-feed.</p> <p>Conclusions</p> <p>The salivary gland transcriptome comprises approximately 38% of the total mosquito transcriptome and a small proportion of it is dynamically changing already at two hours in response to blood feeding. A better understanding of the salivary gland transcriptome and its function can contribute to the development of pathogen transmission control strategies and the identification of medically relevant bioactive compounds.</p

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease