Pseudomonas aeruginosa uses T3SS to inhibit diabetic wound healing

Diabetic foot ulcers are responsible for more hospitalizations than any other complication of diabetes. Bacterial infection is recognized as an important factor associated with impaired healing in diabetic ulcers. Pseudomonas aeruginosa is the most frequently detected Gram‐negative pathogen in diabetic ulcers. P. aeruginosa infection has been shown to impair healing in diabetic wounds in a manner that correlates with its ability to form biofilm. While the majority of infections in diabetic ulcers are biofilm associated, 33% of infections are nonbiofilm in nature. P. aeruginosa is the most prevalent Gram‐negative pathogen in all diabetic wound types, which suggests that the deleterious impact of P. aeruginosa on healing in diabetic wounds goes beyond its ability to form biofilm and likely involves other factors. The Type III Secretion System (T3SS) virulence structure is required for the pathogenesis of all P. aeruginosa clinical isolates, suggesting that it may also play a role in the inhibition of wound repair in diabetic skin ulcers. We evaluated the role of T3SS in mediating P. aeruginosa–induced tissue damage in the wounds of diabetic mice. Our data demonstrate that P. aeruginosa establishes a robust and persistent infection in diabetic wounds independent of its ability to form biofilm and causes severe wound damage in a manner that primarily depends on its T3SS.     

Preoperative duplex ultrasound parameters predicting male fertility after successful varicocelectomy

Objectives:

To assess duplex ultrasound (DUS) parameters, and predicti the outcome of varicocele ligation in male infertility.

Methods:

This retrospective and follow up study was conducted at Dr. Sulaiman Al Habib Hospital, AlQassim, Saudi Arabia between January 2011 and December 2012. Eighty-two patients were selected, who presented with clinical/subclinical varicocele and male infertility. All these patients had DUS of the scrotum and underwent for low ligation varicocelectomy. These patients were followed for a period of 12-24 months after surgery for the occurrence of paternity. We reviewed pre-operative scrotal DUS of these 82 patients for the testicular size and volume, pampiniform veins caliber and duration of reflux in the dilated veins at rest, and after valsalva maneuver. These DUS parameters were correlated with the postoperative paternity rate.

Results:

Postoperative paternity was achieved in 18 patients (31.6%) with normal-sized testes, and in 3 patients (12%) with small size testes. The positive paternity rate was higher (38.5%) in patients with clinically detected varicocele, compared with only 16.7% of patients with subclinical varicocele (detected by ultrasound only). In addition, postoperative paternity was significantly higher in patients with bilateral varicocele (70.6%), with shunt-type varicocele (71.4%), and patients with a permanent grade of venous reflux (62.5%).

Conclusion:

Selection of patients for the successful paternity after varicocele repair depends mainly on DUS parameters, which includes normal size testicles with shunt type of bilateral varicocele and continuous reflux.Varicocele is defined as dilatation of the pampiniform venous plexus draining the testes. It is much more common on the left side compared with the right side, owing to long length of left testicular vein, the acute angle of insertion of left testicular vein into the left renal vein, lack of effective anti-reflux valves, which may transmit the high pressure of renal vein, making left testicular vein more vulnerable to varicocele.1,2 Varicocele is the most frequently identified male factor for infertility, present in up to 40% of cases. Long duration persistent varicocele is associated with adverse effects on sperm count, sperm motility and morphology, decrease testicular size, abnormal testosterone hormone level and decrease pregnancy rates.3-5 Scrotal physical examination is the preferred method for the diagnosis of varicocele. The Dubin grading system classifies the varicocele into 3 grades. Grade 1: varicocele is visible and palpable at rest; Grade 2: varicocele is palpable, but not visible; and Grade 3: varicocele is palpable only during valsalva maneuver. Duplex ultrasound (DUS) allows accurate diagnosis of varicoceles, even subclinical varicocele, which is not apparent on physical examination. Duplex ultrasound is performed at rest and during Valsalva maneuver.6,7 The scrotal vessels are assessed for the degree of dilatation, augmentation and direction of flow during Valsalva and duration of reflux. In this way, CDU is helpful to select the patient for varicocele repair.8-11 Many studies following varicocelectomy have reported approximately 66-70% improvement in semen parameters and 40-60% of patients have increased conception rates.12-15 Although, the outcome and prognosis after varicocelectomy are still controversial, and there are many preoperative parameters that determine the probability of success of the operation.16-18 There is a great need for research to improve preoperative selection of patients with varicocele. This study was carried out to assess the DUS (DUS includes grey scale ultrasound and color doppler ultrasound) parameters including the testicular size, degree of varicocele, type, and duration of reflux that could predict the outcome of varicocele repair in terms of paternity.     

Pattern of drugs use and association with anti-mutated citrullinated vimentin antibody in rheumatoid arthritis

Objectives:

To demonstrate the pattern of disease-modifying antirheumatic drugs (DMARDs) use in Saudi and non-Saudi rheumatoid arthritis (RA) patients, and to evaluate the association of DMARDs use with anti-mutated citrullinated vimentin (anti-MCV) positivity and other factors.

Methods:

Retrospectively, for a period of 7 years (2007-2014), we studied 205 RA patients, at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. All patients used DMARDs. Pattern of use for all 6 DMARDs was almost the same among Saudis and non-Saudis with no significant difference (p>0.05) for each DMARD; MTX was the most commonly used DMARD (71-76%).

Results:

There was no association between anti-MCV positivity and different DMARDs use. Methotrexate was used 76 times as combination, scoring the highest in this respect. There was a significant correlation (p<0.05) between Plaquenil with Methotrexate and with Sulfasalazine; Leflunomide with anti-TNF and with Prednisolone; age with Methotrexate and with Plaquenil; anti-MCV positivity with Prednisolone. Saudi/non-Saudi status showed no correlation with all factors or drugs. There was no significant association between DMARDs and comorbidity.

Conclusion:

Similar to worldwide results, MTX was the most commonly used DMARD; with the addition of anti-TNF to increase the effect, and folic acid to minimize the side effects. In this cohort, the pattern of use for all DMARDs was similar among Saudis and non-Saudis; treatment depended neither on anti-MCV positivity nor on the presence of comorbid conditions. A study of the association of DMARDs with disease activity is recommended.The effective treatment of rheumatoid arthritis (RA) can be achieved by disease-modifying antirheumatic drugs (DMARDs) that decrease joint damage with improvement of symptoms and functional abilities.1 The DMARDs have been classified into synthetic (sDMARDs) and biological.2 The sDMARDs are traditional drugs; such as methotrexate (MTX), sulfasalazine, leflunomide, and hydroxychloroquine (Plaquenil).2 The sDMARDs also include synthetic glucocorticoids (such as Prednisolone).3 If an sDMARDs is not effective after a trial of 3 months,4 they are usually combined with a biological DMARD, such as tumor necrosis factor alpha (TNF-α) blockers.1 To achieve disease remission in approximately 50 of people and improved overall outcomes, the DMARDs should be started very early in the disease.5 The frequently used DMARDs include MTX (the most commonly used one), Plaquenil (hydroxychloroquine), Azulfidine (sulfasalazine), and Arava (leflunomide), either as monotherapy, or in combination.1 Methotrexate is the most commonly used DMARD wordwide,6,7 and is the first line of treatment;8-10 even according to the treatment guidelines from the American College of Rheumatology (2012),11 and the European League Against Rheumatism (2010).12 Methotrexate is usually combined with folic acid (a vitamin),13 in order to reduce its adverse effects including nausea, vomiting or abdominal pain (gastrointestinal), hematologic, pulmonary, and hepatic.10 Methotrexate is teratogenic, thus, pregnancy should be avoided.8,10 Prednisolone (a synthetic glucocorticoids) can be used in the short term, while waiting for slow-onset drugs to take effect,1 and also as an injections into individual joints.1 Although its long-term use reduces joint damage, it also results in osteoporosis and susceptibility to infections, and thus is not recommended.1 A better effect can be achieved by combining MTX with anti-TNF than with MTX monotherapy.14 The response rate is better when switching from MTX monotherapy to MTX plus anti-TNF than combined DMARDs to MTX plus anti-TNF.14 In this study, our aim was to determine the pattern of disease modifying antirheumatic drugs use, and their association with anti-mutated citrullinated vimentin antibody (anti-MCV) in rheumatoid arthritis patients.     

Spontaneous Achilles tendon rupture in alkaptonuria

Alkaptonuria (AKU) is a rare inborn metabolic disease characterized by accumulation of homogentisic acid (HGA). Excretion of HGA in urine causes darkening of urine and its deposition in connective tissues causes dark pigmentation (ochronosis), early degeneration of articular cartilage, weakening of the tendons, and subsequent rupture. In this case report, we present a rare case of a patient presented with unilateral spontaneous rupture of Achilles tendon due to AKU. The patient developed most of the orthopedic manifestations of the disease earlier than typical presentations. Alkaptonuria patients should avoid strenuous exercises and foot straining especially in patients developing early orthopedic manifestations.Alkaptonuria (AKU) is a rare genetic metabolic disorder with an incidence of 1:250,000 in most populations. It is due to deficiency of homogentisate 1,2-dioxygenase (HGD), which is an enzyme involved in the phenylalanine and tyrosine degradation pathway.1,2 Homogentisate 1,2-dioxygenase deficiency results in accumulation of homogentisic acid (HGA), which is oxidized to benzoquinones that polymerize and form a dark pigment. The excess HGA binds to the connective tissues and cartilage. Ochronotic osteoarthropathy is used to refer to the musculoskeletal manifestation of AKU. Ochronosis is the darkening of connective tissues due to the deposition of HGA and/or its polymer in connective tissue. Over time this causes ochronotic osteoarthropathy.3 On microscopic examination yellowish (ocher-like) discoloration of the tissue is seen, but macroscopically the affected tissues appear bluish grey. This leads to weakness and early degeneration of articular cartilage and arthritis.2 Large quantities of HGA excreted in urine causes urine to darken upon standing due to oxidation or after exposure to alkaline agents.1 Rupture of Achilles tendon is an important clinical manifestation of AKU. There are few reports in the literature of spontaneous rupture of the Achilles tendon caused by AKU.4-6 We report a case of an AKU patient presented with a unilateral spontaneous rupture of Achilles tendon. The objective of this case report is to highlight the rare Achilles tendon rupture due to AKU, which can be a reference for physicians and surgeons in the prevention and/or delay of such a complication.     

Transcatheter aortic valve replacement: The year in review 2017

This article is a continuation of our previously published annual reviews of transcatheter aortic valve replacement (TAVR). In 2017, TAVR further established a foothold in the management of intermediate risk patients with the publication of SURTAVI trial. Randomized trials also addressed the use of cerebral protection during TAVR and single versus dual antiplatelet therapy after TAVR. Newer generation valve systems continued to be studied for their efficacy and safety. This paper summarizes the major studies published in 2017.

     

The effect of cannabis on oxidative stress and neurodegeneration induced by intrastriatal rotenone injection in rats

We investigated the effect of cannabis treatment on the development of oxidative stress and nigrostriatal cell injury induced by intrastriatal rotenone injection in rats. Rotenone was injected into the right striatum at a concentration of 5 mM (3 μl/rat). The control rats received the vehicle (DMSO). Subsequently, the effect of Cannabis sativa extract treatment on rotenone toxicity was evaluated. Starting on the second day of rotenone injection, rats were treated with C. sativa extract (5, 10, or 15 mg/kg) (expressed as Δ⁹-tetrahydrocannabinol) subcutaneously (s.c.) once daily for 30 days. Biochemical markers of oxidative stress, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase 1 (PON1) activity, catalase activity, as well as tumor necrosis factor alpha (TNF-α), were determined in different brain areas after 30 days of rotenone treatment. Histopathology and immunohistochemical expression of tyrosine hydroxylase (TH), capase 3, and inducible nitric oxide synthase (iNOS) were also performed. Results showed that intrastriatal injection of rotenone resulted in increased brain oxidative stress in the cerebral cortex, striatum, hippocampus, midbrain, and cerebellum. MDA increased by 41.4–70 %, nitric oxide increased by 48.3–77.5 %, while GSH decreased by 25.0–34.2 %. PON1 and catalase activities decreased by 43.0–60.8 % and by 14.2–36 %, respectively, in these areas. Striatal TNF-α increased by 638.9 % of control value after rotenone injection. Rotenone induced motor deficits (decreased rearing activity). Rotenone caused marked nigrostriatal neurodegeneration, decreased TH immunoreactivity, and increased both iNOS and caspase 3 immunoreactivities in the striatum. Cannabis decreased brain oxidative stress and nitric oxide release induced by intrastriatal rotenone in several brain areas. Cannabis also decreased the elevated TNF-α in the striatum. Cannabis did not protect against the immunohistochemical changes in the striatum and substantia nigra or against neuronal degeneration induced by rotenone treatment. Collectively, these results indicated that the administration of cannabis did not protect against nigrostriatal damage caused by intrastriatal rotenone.     

Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes

OBJECTIVEImpaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management.RESULTSTen subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years.CONCLUSIONSCCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status.