Ligation of the intersphincteric fistula tract procedure and its modifications / Procedimento de ligadura de trato de fístula interesfincteriana e suas modificações

ABSTRACT Purpose: Treatment of anal fistulae is regarded as a challenge due to the diverse nature of this disease and its countless complications. Ligation of the intersphincteric fistula tract procedure and its modifications have been popularized among many surgeons worldwide due to their simplicity and promising outcomes. The main purpose of this article was to conduct a comprehensives review of the published literature on ligation of the intersphincteric fistula tract procedure and its modifications. Method: PubMed, the Cochrane database and Ovid were searched from January 2007 to June 2017. Fully published peer-reviewed studies which applied ligation of the intersphincteric fistula tract procedure and its modifications for the treatment of anal fistulae of cryptogenic origin with follow-up of median 12 months were eligible. Uncompleted studies, case reports, reviews, abstracts, letters, short communication, comments, and studies which did not fulfill inclusion criteria were excluded. The primary outcome was to measure primary healing, overall healing, failure, and recurrence of ligation of the intersphincteric fistula tract procedure and its modifications. Results: Twenty-two studies were identified with only ten studies meeting criteria of inclusion. Original ligation of the intersphincteric fistula tract was performed in five studies with a population of 199 patients while the remaining five studies showed four different modifications of the ligation of the intersphincteric fistula tract with a total number of 147 patients. Both original LIFT and its modifications have promising as well as potentially similar outcomes; primary healing in the original ligation of the intersphincteric fistula tract (73.95%) (95% CI 60.3-85.6) performed less than the modifications (82.3%) (95% CI 64.8-94.7). Overall healing in the original ligation of the intersphincteric fistula tract (78.9%) (95% CI 58.5-93.7) performed relatively less than in the modifications (93.6%) (95% CI 81.4-99.6). Failure in the original ligation of the intersphincteric fistula tract (17.9%) (95% CI 4.9-36.5) performed almost the same as the modifications (17.7%) (95% CI 5.3-35.2). Recurrence in the original ligation of the intersphincteric fistula tract was 9.7% (95% CI 1.7-23.2). However, there was no recurrence in the modifications. Conclusion: Ligation of the intersphincteric fistula tract and its modifications are effective and simple procedures in treating simple anal fistulae, especially high transsphincteric ones. However, more trials should be performed to evaluate its effectiveness regarding complex fistulae.

RESUMO Objetivo: O tratamento de fístulas anais é considerado um desafio devido à natureza diversa dessa doença e suas incontáveis complicações. O procedimento de ligadura do trato da fístula interesfincteriana e suas modificações foi popularizado entre cirurgiões em todo o mundo devido a sua simplicidade e desfechos promissores. O principal objetivo deste artigo foi conduzir uma revisão abrangente da literatura publicada sobre o procedimento de ligadura do trato da fístula interesfincteriana e suas modificações. Método: as bases de dados PubMed, Cochrane e Ovid foram pesquisadas de janeiro de 2007 a junho de 2017. Estudos publicados com revisão por pares que aplicaram o procedimento de ligadura do trato da fístula interesfincteriana e suas modificações para o tratamento de fístulas anais de origem criptogênica com acompanhamento de mediana de 12 meses foram elegíveis. Estudos incompletos, relatos de casos, revisões, resumos, cartas, comunicação breve, comentários e estudos que não preenchiam os critérios de inclusão foram excluídos. O desfecho primário foi medir a cicatrização primária, a cicatrização geral, falhas e recorrência do procedimento de ligadura do trato da fístula interesfincteriana e suas modificações. Resultados: Vinte e dois estudos foram identificados com apenas dez estudos atendendo aos critérios de inclusão. A ligadura original do trato da fístula interesfincteriana foi realizada em cinco estudos com uma população de 199 pacientes, enquanto os cinco estudos restantes apresentaram quatro modificações diferentes da ligadura do trato da fístula interesfincteriana com um total de 147 pacientes. Tanto o LIFT original quanto suas modificações têm resultados promissores e desfechos potencialmente semelhantes; cicatrização primária na ligadura original do trato da fístula interesfincteriana de 73,95% (IC 95% 60,3-85,6) menos realizada que as modificações de 82,3% (IC 95% 64,8-94,7). Cicatrização geral na ligadura original do trato da fístula interesfincteriana de 78,9% (IC 95% 58,5-93,7) realizada relativamente menos do que as modificações (93,6%, IC 95% 81,4-99,6). A falha na ligadura original do trato da fístula interesfincteriana (17,9%; IC 95% 4,9-36,5) realizada quase tanto quanto as modificações (17,7%; IC 95% 5,3-35,2). Recidiva na ligadura original do trato da fístula interesfincteriana em 9,7% (IC 95% 1,7-23,2). No entanto, não houve recorrência nas modificações. Conclusão: A ligadura do trato da fístula interesfincteriana e suas modificações são procedimentos eficazes e simples no tratamento de fístulas anais simples, especialmente as transesfincterianas altas. No entanto, mais estudos devem ser realizados para avaliar sua eficácia em relação às fístulas complexas.

Isolation and characterization of native Bacillus thuringiensis strains from Saudi Arabia with enhanced larvicidal toxicity against the mosquito vector Anopheles gambiae (s.l.).

BACKGROUND: Worldwide, mosquito vectors are transmitting several etiological agents of important human diseases, including malaria, causing millions of deaths every year. In Saudi Arabia, as elsewhere, vector-control is based mostly on chemical insecticides which may be toxic and cause environmental deprivation. Here, to support the development of bio-pesticide alternatives, a study was conducted to identify native Bacillus thuringiensis (Bt) isolates with improved toxicity against the malaria vector, Anopheles gambiae (s.l.). METHODS: Sixty-eight Bt isolates were obtained from 300 soil and other samples collected from 16 sites across Saudi Arabia. Bt identification was based on morphological characteristics of colonies, shape of parasporal crystals and biochemical profiles. After characterization of their mosquitocidal activity, larvicidal strains were described through 16S ribosomal DNA gene sequencing, cry, cyt and chi genes PCR-amplification profiles, and SDS-PAGE protein analyses. RESULTS: Spherical Bt crystals were predominant amongst the 68 isolates (34%), while irregular, bi-pyramidal and spore-attached crystals were found in 32, 13 and 21% of strains, respectively. LC50 and LC90 bioassays showed that 23/68 isolates were larvicidal, with distinct biochemical activity profiles compared to non-larvicidal Bt strains. Eight larvicidal strains showed larvicidal activity up to 3.4-fold higher (LC50 range: 3.90-7.40 µg/ml) than the reference Bti-H14 strain (LC50 = 13.33 µg/ml). Of these, 6 strains had cry and cyt gene profiles similar to Bti-H14 (cry4Aa, cry4Ba, cry10, cry11, cyt1Aa, cyt1Ab, cyt2Aa). The seventh strain (Bt63) displaying the highest larvicidal activity (LC50 = 3.90 µg/ml) missed the cry4Aa and cyt1Ab genes and had SDS-PAGE protein profiles and spore/crystal sizes distinct from Bti-H14. The eight strain (Bt55) with LC50 of 4.11µg/ml had cry and cyt gene profiles similar to Bti-H14 but gave a chi gene PCR product size of 2027bp. No strains harbouring cry2, cry17 + 27, cry24 + 40, cry25, cry29, cry30, or cyt2Ba were detected. CONCLUSION: This study represents the first report of several Saudi indigenous Bt strains with significantly higher larvicidal efficacy against An. gambiae than the reference Bti-H14 strain. The very high toxicity of the Bt63 strain, combined with distinct cry and cyt genes and SDS-PAGE-protein profiles makes it a promising candidate for future applications in mosquito bio-control.

Potential effects of samsum ant, Brachyponera sennaarensis, venom on TNF-α/NF-κB mediated inflammation in CCL4-toxicity in vivo.

BACKGROUND: Ant venom shows antimicrobial, anti-parasitic and anti-inflammatory activities, both in vitro and in vivo. Our recent studies have confirmed the role of samsum ant venom (SAV) as a powerful antioxidant. This study aimed to investigate whether SAV as a potential treatment for CCl4-induced acute liver toxicity in an animal (rat) model. METHODS: Thirty-two rats were assigned into four groups; the first one served as the control. The second group received a single dose of 1 ml/kg CCl4 in a 1:1 ratio with olive oil through an intraperitoneal injection. The third group received a single dose of 1 ml/kg CCl4 and then treated with SAV at a dose of 100 µg SAV twice a week for three weeks. The fourth group received a dose of 100 µg SAV only twice a week for three weeks. ELISA, RT-PCR and histopathological examinations were applied. RESULTS: Results showed that antioxidant enzymes were significantly reduced in the diseased animals. SAV was found to significantly restore the oxidative stability in diseased animals. ELISA estimation and RT-PCR analysis also showed significant upregulation of both nuclear factor (κB) NF-κB and inhibitor (κB) IκB, respectively, in the diseased animals compared to the normal ones. The expression of tumour necrosis factor alpha (TNF-α) and pro-apoptotic receptor (Fas) were also significantly up-regulated in the diseased rats. Interestingly, SAV was found to significantly restore NF-κB, IκB and TNF-α in the diseased rats to the normal values. As a result, liver enzymes, serum proteins and lipid concentrations were significantly improved by SAV in CCl4-animals in comparison with the control ones. Moreover, SAV obviously improved the hepatic tissues of the same group was. CONCLUSION: SAV treatment restores the normal biochemical and oxidative stability by improving the TNF-α/NF-κB mediated inflammation in CCL4-treated rats.

Wound healing of different molecular weight of hyaluronan; in-vivo study.

Recruitment of cells and mediators is altered during impaired wound healing, thereby delaying this process. To overcome this problem, the correlation of wound healing in older rats, and the impact of different molecular weight of hyaluronan without silver nanoparticles; (low-HA1), (High-HA2), (Medium- HA3) and with silver nanoparticles (High-HA4) is investigated. The superior HA were selected to be further investigated onto diabetic wounds. Our results pointed to a marked deficiency in wounds granulation in older rats, which was accompanied with impairment of healing process. In older rats group treated with HA2 or HA4, granulation and dermal construction were improved. Furthermore, the number of pathogenic bacteria on wounds was declined throughout the first 24h by HA2 and HA4. The wound size in HA4-treated older rats was significantly smaller than that in other HA1, HA2 or HA3-treated older ones. Also, diabetes impaired the level of inflammatory cytokine, in diabetic model. On contrary, HA4 was found to normalize the level of inflammatory cytokine, in the diabetic model. Furthermore, HA4 was found to recover all oxidative and toxicity markers in diabetic models. This data confirms the critical role of HA4 to improve granulation and inflammatory mediators in impaired older and diabetic rat wound healing.

Up-regulation of Hsp72 and keratin16 mediates wound healing in streptozotocin diabetic rats.

BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP) was able to regulate wound healing normally in streptozotocin (STZ)-diabetic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72) and keratin16 (Krt16) expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.

Camel milk peptide improves wound healing in diabetic rats by orchestrating the redox status and immune response.

BACKGROUND: Diabetes mellitus alters oxidative stability and immune response. Here, we investigated the impact of a peptide extracted from camel milk (CMP) on the oxidative status, transcription factor kappa-B (NF-kB) and inflammatory cytokine in diabetic wounds. METHODS: Rats were assigned into three groups: control, diabetic induced (DM) and diabetic induced with multiple doses of CMP for a week (DM-CMP). RESULTS: DM showed a sharp decline in the activity of major antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) compared to the control. The DM-CMP group, however, showed a noticeable replenishment in the activity of these enzymes compared to the DM group. The CMP-treated group also showed a normal level of lipid peroxidation marker (MDA) compared to the DM rats. Furthermore, ELISA analysis of serum TNF-α protein showed an elevated level in diabetic rats in comparison to control serum. However, RT-PCR analysis of locally wounded skin tissues revealed that diabetes down-regulates the RNA expression of both TNF-α and MIF genes in comparison to the control samples but that CMP was found to restore RNA expression significantly. Although it was elevated in CMP-treated rats after one day of wound incision, the NF-kB protein level was significantly decreased seven days after the incision in comparison to the animals in the diabetic group. CONCLUSION: CMP, therefore, can be seen an effective antioxidant and immune stimulant that induces oxidative stability and speeds up wound healing in diabetic model animals, making it a potential adjuvant in improving wound healing in those with diabetic conditions.

Neurochemical, structural and neurobehavioral evidence of neuronal protection by whey proteins in diabetic albino mice.

BACKGROUND: Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS. METHODS: Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP). RESULTS: The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure. CONCLUSION: The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.

Up-regulation of Hsp72 and keratin16 mediates wound healing in streptozotocin diabetic rats

BACKGROUND: Impaired wound healing is a complication of diabetes and a serious problem in clinical practice. We previously found that whey protein (WP) was able to regulate wound healing normally in streptozotocin (STZ)-dia-betic models. This subsequent study was designed to assess the effect of WP on heat shock protein-72 (Hsp72) and keratin16 (Krt16) expression during wound healing in diabetic rats. METHODS: WP at a dosage of 100 mg/kg of body weight was orally administered daily to wounded normal and STZ-diabetic rats for 8 days. RESULTS: At day 4, the WP-treated diabetic wound was significantly reduced compared to that in the corresponding control. Diabetic wounded rats developed severe inflammatory infiltration and moderate capillary dilatation and regeneration. Treated rats had mild necrotic formation, moderate infiltration, moderate to severe capillary dilatation and regeneration, in addition to moderate epidermal formation. Hsp72 and Krt16 densities showed low and dense activity in diabetic wounded and diabetic wounded treated groups, respectively. At day 8, WP-treatment of diabetic wounded animals revealed great amelioration with complete recovery and closure of the wound. Reactivity of Hsp72 and Krt16 was reversed, showing dense and low, or medium and low, activity in the diabetic wounded and diabetic wounded treated groups, respectively. Hsp72 expression in the pancreas was found to show dense reactivity with WP-treated diabetic wound rats. CONCLUSION: This data provides evidence for the potential impact of WP in the up-regulation of Hsp72 and Krt16 in T1D, resulting in an improved wound healing process in diabetic models.

Amino acids content and electrophoretic profile of camel milk casein from different camel breeds in Saudi Arabia.

This study aimed to evaluate amino acids content and the electrophoretic profile of camel milk casein from different camel breeds. Milk from three different camel breeds (Majaheim, Wadah and Safrah) as well as cow milk were used in this study. Results showed that ash and moisture contents were significantly higher in camel milk casein of all breeds compared to that of cow milk. On the other hand, casein protein of cow milk was significantly higher compared to that of all camel milk breeds. Molecular weights of casein patterns of camel milk breeds were higher compared to that of cow milk. Essential (Phe, Lys and His) and non-essential amino acids content was significantly higher in cow milk casein compared to the casein of all camel milk breeds. However, there was no significant difference for the other essential amino acids between cow casein and the casein of Safrah breed and their quantities in cow and Safrah casein were significantly higher compared to the other two breeds. Non-essential amino acids except Arg and the essential amino acids (Met, Ile, Lue and Phe) were also significantly higher in cow milk α-casein compared to α-casein from all camel breeds. Moreover, essential amino acids (Val, Phe and His) and the non-essential amino acids (Gly and Ser) content was significantly higher in cow milk ß-casein compared to the ß-casein of all camel milk breeds and the opposite was true for Lys, Thr, Met and Ile. However, Met, Ile, Phe and His were significantly higher for ß-casein of Majaheim compared to the other two milk breeds. The non-essential amino acids (Gly, Tyr, Ala and Asp) and the essential amino acids (Thr, Val and Ile) were significantly higher in cow milk κ-casein compared to that for all camel milk breeds. There was no significant difference among all camel milk breeds in their κ-casein content of most essential amino acids. Relative migration of casein bands of camel milk casein was not identical. The relative migration of αs-, ß- and κ-casein of camel casein was slower than those of cow casein. The molecular weights of αs-, ß- and κ-casein of camel caseins were 27.6, 23.8 and 22.4 KDa, respectively. More studies are needed to elucidate the structure of camel milk.

Whey protein enhances normal inflammatory responses during cutaneous wound healing in diabetic rats.

BACKGROUND: Prolonged wound healing is a complication of diabetes that contributes to mortality. Impaired wound healing occurs as a consequence of excessive reactive oxygen species (ROS) production. Whey protein (WP) is able to reduce the oxygen radicals and increase the levels of the antioxidant glutathione. Thus, the aim of this study was to determine whether dietary supplementation with WP could enhance normal inflammatory responses during wound healing in diabetic rats. Animals were assigned into a wounded control group (WN), a wounded diabetic group (WD) and a wounded diabetic group orally supplemented with whey protein (WDWP) at a dose of 100 mg/kg body weight. RESULTS: Whey protein was found to significantly decrease the levels of malondialdehyde (MDA), nitric oxide (NO) and ROS. A significant restoration of the glutathione level was observed in WDWP rats. During the early wound healing stage, IL-1ß, TNF-α, IL-6, IL-4 and neutrophil infiltration were significantly decreased in WD mice. WP supplementation was found to restore the levels of these inflammatory markers to the levels observed in control animals. In addition, the time required for wound healing was significantly prolonged in diabetic rats. WP was found to significantly decrease the time required for wound healing in WDWP rats. CONCLUSION: In conclusion, dietary supplementation with WP enhances the normal inflammatory responses during wound healing in diabetic mice by restoring the levels of oxidative stress and inflammatory cytokines.

Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice.

BACKGROUND: Long and persistent uncontrolled diabetes tends to degenerate the immune system and leads to an increased incidence of infection. Whey proteins (WPs) enhance immunity during early life and have a protective role in some immune disorders. In this study, the effects of camel WP on the chemotaxis of B and T cells to CXCL12 and CCL21 in diabetic mice were investigated. RESULTS: Flow cytometric analysis of the surface expressions of CXCR4 (CXCL12 receptor) and CCR7 (CCL21 receptor) on B and T cells revealed that the surface expressions of CXCR4 and CCR7 were not significantly altered in diabetic and WP-supplemented diabetic mice compared with control mice. Nevertheless, B and T lymphocytes from diabetic mice were found to be in a stunned state, with a marked and significant (P < 0.05) decrease in CXCL12- and CCL21-mediated actin polymerization and subsequently, a marked decrease in their chemotaxis. WP supplementation in the diabetes model was found to significantly increase CXCL12- and CCL21-mediated actin polymerization and chemotaxis in both B and T cells. CONCLUSION: Our data revealed the benefits of WP supplementation in enhancing cytoskeletal rearrangement and chemotaxis in B and T cells, and subsequently improving the immune response in diabetic mice.