Ipsilateral fracture dislocations of the hip and knee joints with contralateral open fracture of the leg: a rare case and its management principles

This paper discussed the injury mechanism and management of a patient who had concomitant ipsilateral hip and knee dislocations and contralateral open leg fracture.A 32-year-old man presented with ipsilateral fracture-dislocations of the left hip (Pipkin's type IV) and knee (Moore II) joints and contralateral open fracture of the leg bones after a car accident. After emergency resuscitative measures, the hip joint was reduced and Pipkin's fracture was fixed using Ganz approach with lag screws; knee joint was reduced closely and tibial plateau fracture was stabilized with lateral buttress plate and a transarticular spanning fixator. The open fracture on the other leg was de-brided and fixed with an external fixator. There was no instability in both joints after fixation when he was examined under anesthesia. The fractures united after 3 months and the patient had no residual instability of hip and knee. There was no clinical or radiological evidence of osteonecrosis in the hip joint after 6 months. At one-year follow-up, he had satisfactory functional outcome with almost normal range of motion at both joints.Ipsilateral hip and knee dislocations are rare injuries and more caution is needed for early diagnosis. A timely appropriate intervention can provide good functional outcome to the patient in this situation.     

A Child Presenting with Recurrent Corneal Ulcers: Hereditary Sensory and Autonomic Neuropathy IV (HSAN IV)

Hereditary Sensory and Autonomic Neuropathy IV (HSAN IV) or Congenital Insensitivity to pain and Anhidrosis is an autosomal recessive condition. It is characterized by absence of reaction to painful stimuli, anhidrosis, self-mutilating behaviour and episodic fever. We report a child with HSAN IV who presented primarily with recurrent corneal ulcers and the classical history helped us clinch the diagnosis. Molecular testing revealed a homozygous pathogenic frameshift mutation in NTRK1 c.717delG, p.(Met239fs). Molecular testing is confirmatory and this will help the family in future prenatal diagnosis.     

Rescuing CD4+CD25+ regulatory T-cell functions in rheumatoid arthritis by cytokine-targeted monoclonal antibody therapy

CD4+CD25+ regulatory T cells (Tregs) play a crucial role in controlling the development of autoimmune diseases such as rheumatoid arthritis (RA). However, despite an increased number of Tregs, the persistence of inflammation in the rheumatoid joints suggests that Tregs are unable to suppress ongoing disease, perhaps due to an inhibition of their functions by pro-inflammatory cytokines. Treatment of RA patients with anti-TNF-alpha monoclonal antibodies such as infliximab and adalimumab has been found to induce and restore the functions of Tregs. Thus, manipulation of the pro-inflammatory environment in the inflamed synovia via neutralization of inflammatory cytokines by monoclonal antibodies could represent a novel therapeutic strategy for restoring the suppressive functions of Tregs and induction and/or expansion of Tregs in order to reinforce tolerance mechanisms.     

A biosynthetic pathway generating 12-hydroxy-5,8,14-eicosatrienoic acid from arachidonic acid is active in mouse skin microsomes

The epidermis expresses cyclooxygenases, lipoxygenases, and cytochromes P450, which utilize arachidonic acid to generate a diverse array of lipid mediators affecting epidermal cellular differentiation and functions. Recent studies show that mouse epidermis expresses CYP2B19, a keratinocyte-specific epoxygenase that generates 11,12- and 14,15-epoxyeicosatrienoic (EET) acids from arachidonate. We studied CYP2B19-dependent metabolism in mouse epidermal microsomes, reconstituted in the presence of [1-(14)C]arachidonic acid. The majority of the (14)C products formed independently of NADPH, indicative of robust epidermal cyclooxygenase and lipoxygenase activities. We studied two NADPH-dependent products generated in a highly reproducible manner from arachidonate. One of these (product I) coeluted with the CYP2B19 product 14,15-EET on a reversed-phase high-performance liquid chromatography (HPLC) system; there was no evidence for other regioisomeric EET products. Further analyses proved that product I was not an epoxy fatty acid, based on different retention times on a normal-phase HPLC system and failure of product I to undergo hydrolysis in acidic solution. We analyzed purified epidermal (14)C products by liquid chromatography negative electrospray ionization mass spectrometry. Structures of the NADPH-dependent products were confirmed to be 12-oxo-5,8,14-eicosatrienoic acid (I) and 12-hydroxy-5,8,14-eicosatrienoic acid (II). This was the first evidence for a 12-hydroxy-5,8,14-eicosatrienoic acid biosynthetic pathway in mouse epidermis. Epidermal microsomes also generated 12-hydroperoxy, 12-hydroxy, and 12-oxo eicosatetraenoic acids from arachidonate, possible intermediates in the 12-hydroxy-5,8,14-eicosatrienoic acid biosynthetic pathway. These results predict that hydroxyeicosatrienoic acids are synthesized from arachidonate in human epidermis. This would have important implications for human skin diseases given the known pro- and anti-inflammatory activities of stereo- and regioisomeric hydroxyeicosatrienoic acids.     

Endovascular stent implantation in the coeliac and superior mesenteric arteries in the treatment of chronic mesenteric ischemia

Mesenteric ischemia is a rare but serious cause of abdominal pain.We present the case of a man who had symptomatic mesenteric ischemia, secondary to a superior mesenteric artery stenosis in conjunction with a coeliac artery stenosis. He was treated with balloon angioplasty and stent insertion, and showed good symptomatic improvement.     

Cardiovascular and renal pathologic implications of prorenin, renin, and the (pro)renin receptor: promising young players from the old renin-angiotensin-aldosterone system

The overactivation of the renin–angiotensin–aldosterone system accounts for many cardiovascular and renal abnormalities. At several levels of its cascade, the renin–angiotensin–aldosterone system can be efficiently inhibited, of which interruption of the generation of angiotensin I by renin inhibition is considered most efficacious. All of these interruptions (renin inhibition, angiotensin-converting enzyme inhibition, and AT1 receptor blockade) increase plasma renin levels by inhibiting the negative feedback loop exerted by angiotensin II on renin production. Recent studies show that both prorenin and renin activate angiotensin II-independent signaling cascade through (pro)renin receptor, a new-fangled player of the old renin-angiotensin-aldosterone system. The probable mechanisms by which prorenin, renin, and (pro)renin receptors are functionally interrelated in pathophysiological conditions have been debated over the past decade without satisfactory conclusion. We revisited these areas and critically examined the relationship between elevated levels of circulating prorenin and renin-induced activation of the (pro)renin receptor and incidences of hypertension and end-organ damage. The complexity of the (pro)renin receptor has grown up with recent reports that this multifunctional receptor is a component of the Wnt receptor complex. This complexity and the receptor's function as an adaptor between the Wnt receptor and the vacuolar H+-ATPase complex has also been addressed in this review.     

Paclitaxel loaded carrier based biodegradable polymeric implants: Preparation and in vitro characterization

The objective of this study was to develop paclitaxel (PTX) loaded poly(ε-caprolactone) (PCL) based tiny implants. β-Cyclodextrin (β-CD) and polyethylene glycol (PEG 6000) were used to enhance solubility and release of the drug in the phosphate buffer saline pH 7.4. Implants were evaluated in terms of color, shape, thickness, surface area, weight, drug content. Developed implants were characterized for their surface morphology (SEM analysis), drug physical state by thermal analysis (DSC studies), crystalline nature (XRD studies) and drug excipients compatibility (FT-IR spectroscopy). Macroscopically all the tiny implants were white in color and cylindrical in shape with smooth surfaces. PTX was entrapped within implants in the polymeric amorphous form. In vitro drug release studies showed prolonged and controlled release of PTX with zero order and Korsmeyer–Peppas model being exhibited. Excipients and method of preparation did not affect chemical stability of PTX.     

Human mesenchymal stem cells overexpressing therapeutic genes: from basic science to clinical applications for articular cartilage repair

Adult articular cartilage has a limited capacity for self repair. Reproduction of a native structure and functional integrity in damaged cartilage remains a major problem in orthopaedic surgery. Strategies based on the implantation of genetically modified cells to sites of injury may provide workable options to treat articular cartilage lesions like those resulting from acute trauma or associated with the progression of osteoarthritis. Mesenchymal stem cells have remarkable properties that make them an attractive source of cells to treat cartilage disorders due to their self-renewal capability, stemness maintenance, and chondrogenic differentiation potential. For these reasons, such progenitor cells might be further modified by gene transfer protocols to reinforce their potency and consequently, to enhance the healing processes in damaged tissue following transplantation in sites of cartilage injury. Here, we propose an overview of the current approaches employed for cell- and gene-based treatment of articular cartilage disorders using mesenchymal stem cells.