Topical tacrolimus therapy in the management of lower extremity ulcers due to prolidase deficiency

Prolidase deficiency is a rare autosomal recessive disorder characterized by cutaneous ulcers, facial dysmorphism, recurrent infections, and intellectual disability. We report a unique case of a 6‐year‐old boy with prolidase deficiency and Crohn's disease who presented with lower extremity ulcers. Cutaneous ulcers due to prolidase deficiency are historically resistant to treatment, and we report success with the novel use of topical tacrolimus.     

The effect of bracing on proprioception of knees with anterior cruciate ligament injury.

This paper is a comprehensive review on the effect of bandaging, bracing, and neoprene sleeves on knee proprioception following anterior cruciate ligament (ACL) injury and reconstruction with a focus on studies that have measured joint position sense and threshold to detection of passive knee motion. Disruption of the ACL does not appear to alter joint position sense soon after injury, although there is evidence that in some subjects deterioration may occur over time. An ACL tear creates a deficit in the threshold to detection of passive knee motion soon after injury and in those with chronic tears. The magnitude of worsening is less then 1.0 degree of movement in flexion-extension and of questionable concern from a clinical and functional perspective. Application of a functional brace or neoprene sleeve to the ACL-deficient limb does not improve the threshold to detection of passive knee motion; however, application of an elastic bandage to a knee with an ACL tear improves joint position sense. Reconstruction of a torn ACL is associated with a deficit in the threshold to detection of passive knee motion, and during the first year of healing the use of a neoprene sleeve provides improvement. Two years following ACL reconstruction there is no deficit in the threshold to detection of passive knee motion and the use of a brace has no effect on this outcome.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Engineering human immunodeficiency virus 1 protease heterodimers as macromolecular inhibitors of viral maturation.

Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defective monomers. A structure-based approach was used to identify amino acid substitutions at the dimer interface of HIV-1 PR that facilitate preferential association of heterodimers and inhibit self-association of the defective monomers. Expression of the designed PR monomers inhibits activity of wild-type HIV-1 PR and viral infectivity when assayed in an ex vivo model system. These results show that it is possible to design PR monomers as macromolecular inhibitors that may provide an alternative to small molecule inhibitors for the treatment of HIV infection.     

Determination of D-sorbitol in human erythrocytes by an improved enzymatic method with fluorometric detection

In this enzymatic method to analyze erythrocytes for D-sorbitol, the erythrocytes were separated from plasma by centrifugation, washed with isotonic saline (9 g/L NaCl), then diluted threefold with more saline. We lysed 1.5 mL of the diluted erythrocytes with chloroform and precipitated the protein with 58 g/L HClO4 solution. The resulting supernates were mixed with buffer, NAD+, and sorbitol dehydrogenase (EC 1.1.1.14). For standards, we added sorbitol to the erythrocytes before lysing. After 25 min of incubation at 37 degrees C, the fluorescence responses were recorded. Results for sorbitol were corrected for sample-blank and enzyme fluorescence, and were then normalized for hemoglobin content. Response was linear for a sorbitol concentration range of 1 to 30 mumol/L. Reproducibility was good, with an average CV of 2.5% at 10 mumol/L. Results for healthy individuals and diabetic patients are presented.     

Innate immunity and its role against infections.

LEARNING OBJECTIVES: This article reviews current concepts of the innate immune system that offers protection against infections. It offers an overview for the readers to understand how innate immunity, consisting of different receptors, cells, and mediators recognizes pathogens and exerts protective function against pathogens. DATA SOURCES AND STUDY SELECTION: MEDLINE-search articles including original research papers, review articles, textbooks, and references identified from bibliographies of relevant articles. RESULTS AND CONCLUSIONS: The innate immune system is nonspecific immunity present since birth not requiring repeated exposure to pathogens. It is capable of differentiation between self and nonself. Because of its nonspecificity, it has a broad spectrum of resistance to infection. Further, it is thought to play an important role in the control of adaptive immunity by regulating co-stimulatory molecules and effector cytokines. Innate immunity includes pattern recognition molecules/receptors, antimicrobial peptides, the complement system, inflammatory mediators, and cytokines produced by immune cells. Pattern recognition molecules/receptors recognize pathogen-associated molecular patterns that are essential for microorganisms' survival and pathogenicity. Although innate immunity has recently gained increasing importance, further studies are necessary for a better understanding of its role.     

Non-A Non-B Hepatitis and the Safety of Intravenous Immune Globulin, pH 4.2: A Retrospective Survey:

Abstract. Evidence for transmission of non-A non-B hepatitis (NANB) was sought in 41 patients with primary immune deficiency who were receiving human intravenous immune globulin (IGIV) over periods ranging from 6 to 15 months at a monthly dosage of 400 mg/kg body weight. One lot of a reduced and alkylated IGIV and three lots of a nonmodified preparation stabilized at pH 4.2 were used. No evidence of NANB was found, although transient elevations in serum glutamic pyruvic transaminase (alanine aminotransferase) were found in 6 of the patients. The possible causes of the elevated levels in these 6 patients are discussed.     

A placebo-controlled trial of light treatment for winter depression.

We studied 32 patients with winter seasonal affective disorder (SAD) in a counterbalanced crossover design comparing 1 h of morning light treatment (about 7000 lux) to 1 h of morning placebo treatment (deactivated negative ion generator). Both treatments significantly reduced depression ratings, but there was no difference between the antidepressant response to light and to placebo. Several possible explanations for this result were discussed including an inadequate 'dose' of light (e.g., ineffective duration or intensity), an unusual sample of patients, and a placebo mechanism.