No abstract

Limited information is available on the role of MAPK phosphatase1 (MKP1) signaling in osteoblasts. We have recently reported distinct roles for MKP1 during osteoblast proliferation, differentiation and skeletal responsiveness to parathyroid hormone (PTH). Since MKP1 regulates the phosphorylation status of MAPKs we investigated the involvement of P-ERK and P-p38 MAPKs in MKP1 knock out (KO) early and mature osteoblasts with respect to mineralization and PTH response. Calvarial osteoblasts from 9–14 week old wild type (WT) and MKP1 KO male and female mice were examined. Western blot analysis revealed down-regulation and sustained expressions of P-ERK and P-p38 with PTH treatment in differentiated osteoblasts derived from KO males and females respectively. Exposure of early osteoblasts to p38 inhibitor, SB203580 (S), markedly inhibited mineralization in WT and KO osteoblasts from both genders as determined by von Kossa assay. In osteoblasts from males, ERK inhibitor U0126 (U), not p38 inhibitor (S), prevented the inhibitory effects of PTH on mineralization in early or mature osteoblasts. In osteoblasts from KO females, PTH sustained mineralization in early osteoblasts and decreased mineralization in mature cells. This effect of PTH was attenuated by S in early osteoblasts, and by U in mature KO cells. Changes in matrix gla protein (MGP) expression with PTH in KO osteoblasts did not correlate with mineralization, indicative of MKP1 dependent additional mechanisms essential for PTH action on osteoblast mineralization. We conclude that PTH regulation of osteoblast mineralization in female mice is maturation stage specific and involves MKP1 modulation of P-ERK and P-p38 MAPKs.

Traumatic through-knee or transfemoral amputations with concomitant ipsilateral femoral fractures are extremely rare injuries. The initial goal of management is patient resuscitation and stabilization. Subsequent interventions focus on limb salvage and the creation of a residual limb that can be fitted successfully for a functional lower extremity prosthesis. We present the case of a patient who sustained a traumatic through-knee amputation ipsilateral to an open comminuted femoral fracture. Soft tissue injury prohibited initial primary closure over the distal femoral condyles. A functional residual limb was achieved with acute femoral shortening, maintenance of the femoral condyles and fracture stabilization with a short retrograde intramedullary nail. This approach allowed maintenance of muscular attachments to the femur, soft tissue closure and resulted in a residual limb of acceptable length with a broad weight-bearing surface that was fitted with a prosthesis successfully.

Capgras Syndrome is a subcategory of delusional disorder. People affected by this syndrome believe that a close associate such as a friend or family member has been replaced by an identical imposter. This case report describes a 23-year-old woman with no prior psychiatric history, whom developed Capgras syndrome, via folie a deux, in the setting of poly-substance use. In this patient, a combination of Aripiprazole 10 mg daily and Escitalopram 10 mg daily were effective in resolving symptoms. Clonazepam was utilized for anxiety and Omega-3 fatty acids 1 g for anti-oxidative effects. Further studies are needed to investigate the effects of a variety of causes and treatments for Capgras Syndrome.

Purpose Since the development of antipsychotic drugs in the 1950s, a variety of studies and case reports have been published that suggest an association between exposure to typical antipsychotics and venous thromboembolisms (VTE). Therefore, when starting treatment with antipsychotics, especially low-potency typical antipsychotics and clozapine, health-care providers must account for the patient’s existing VTE risk factors. Design/methodology/approach In this case report, the authors describe the development of a pulmonary embolism associated with use of chlorpromazine in the treatment of an acute manic episode in a 51-year-old female patient with bipolar disorder type 1. Findings The patient was brought to the emergency room by the police on a legal hold for bizarre behaviors at a bus stop, which included incessantly yelling at bystanders. The patient was found to have disorganized thoughts, poor sleep, rapid speech, labile mood, distractibility, auditory hallucinations and grandiose delusions. During the course of her stay, the patient received extensive IM chlorpromazine for extreme agitation, in addition to chlorpromazine 200 mg IM Q8H, which was later decreased to chlorpromazine 100 mg chlorpromazine IM/PO Q8H. On day 4 of the treatment, the patient experienced difficulty breathing, hypoxia and tachycardia and was found to have bilateral expiratory wheezes. CT angiography showed sub-segmental pulmonary embolus and the patient was transferred to MICU service. The patient was then intubated and started on heparin by the medical team. Over the course of the next day, her respiratory distress resolved and the patient was extubated. Originality/value It is possible that chlorpromazine may indeed increase VTEs, and there are various physiological postulations regarding the mechanism of action. However, multiple confounding variables existed in the authors’ report, including venous stasis and the use of restraints, tobacco and valproic acid. Each of these variables has been shown to increase VTE occurrence. Further controlled studies are necessary to identify the true relationship between antipsychotics and VTEs.