Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids

The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl > butyroyl > caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids. These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.     

An Acute Myocardial Infarction Case that Survived An Out‐of‐Hospital Cardiac Arrest in Which Prominent Ischemic J Waves Were Documented

We describe a case of a myocardial infarction, in which prominent ischemic J waves were documented during recurrent ventricular fibrillation attacks. The patient was referred to our hospital to treat an out‐of hospital cardiac arrest. Although the 12‐lead electrocardiogram obtained just after the first cardioversion did not show any apparent J waves, a J wave‐like steep downsloping type ST‐segment elevation associated with q waves in the inferior leads was documented during multiple episodes of ventricular fibrillation. Our report revealed the appearance of J waves as an important marker for lethal arrhythmias in acute ischemia. (PACE 2012; 35:e27–e30)     

Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Hasegawa T, Okamoto A, Kamimura T, Tatsuno I, Hashikawa S‐N, Yabutani M, Matsumoto M, Yamada K, Isaka M, Minami M, Ohta M. Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients. APMIS 2010; 118: 167–78. Streptococcal toxic shock syndrome (STSS) is a re‐emerging infectious disease in Japan and many other developed countries. Epidemiological studies have revealed that the M1 serotype of Streptococcus pyogenes is the most dominant causative isolate of STSS. Recent characterization of M1 isolates revealed that the mutation of covS, one of the two‐component regulatory systems, plays an important role in STSS by altering protein expression. We analyzed the M1 S. pyogenes clinical isolates before or after 1990 in Japan, using two‐dimensional gel electrophoresis (2‐DE) and pulsed‐field gel electrophoresis (PFGE). PFGE profiles were different between the isolates before and after 1990. Markedly different profiles among isolates after 1990 from STSS and pharyngitis patients were detected. Sequence analysis of two‐component regulatory systems showed that covS mutations were detected not only in STSS but also in three pharyngitis isolates, in which proteins from the culture supernatant displayed the invasive type. The mutated CovS detected in the pharyngitis isolates had impaired function on the production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2‐DE. These results suggest that several covS mutations that lead to the malfunction of the CovS protein occurred even in pharyngeal infection.     

EFFECT OF A CALCIUM ENTRY BLOCKER ON BLOOD PRESSURE, PLASMA RENIN ACTIVITY, ALDOSTERONE AND CATECHOLAMINES IN NORMOTENSIVE SUBJECTS

The effects of the calcium entry blocker nifedipine on blood pressure, heart rate, plasma renin activity, aldosterone, noradrenaline and adrenaline were studied in 23 normotensive subjects in the supine and upright positions. Nifedipine, 10 mg administered sublingually, lowered mean blood pressure and increased heart rate, plasma noradrenaline and renin activity without increasing plasma aldosterone in the supine position. The increase in plasma aldosterone in response to upright posture was inhibited by nifedipine, whereas the rise in plasma noradrenaline was augmented. These results suggest that intracellular calcium is important as a regulator of aldosterone secretion as well as of vascular tone in normotensive subjects.     

Identification of two novel mutations in non-Jewish factor XI deficiency

Summary. We have studied two heterozygous unrelated CRM non-Jewish FXI-deficient patients. Neither of the patients carries a previously described mutation. Their FXI genes were screened by SSCP analysis following PCR amplification of each exon and the flanking intronic sequences. DNA fragments showing aberrant mobility were cloned and sequenced. The following mutations were identified: in case 1, a T to G transition in exon 12 results in the substitution of Phe-442 by Val (FXI-F442V); in case 2 a C to A transition in exon 5 results in the substitution of Cys-128 by a nonsense codon (FXI-C128X). The missense mutation results in a substitution within the protease domain of FXI. Molecular modelling locates this residue in a structurally conserved region of the protease domain and the amino acid substitution may therefore interfere with either chain folding and subsequent secretion or the stability of the protein in plasma. We conclude that the mutations which we have identified are responsible for the inherited abnormality in these patients.     

Small renal oncocytoma with central cystic degeneration

A case of a small renal oncocytoma with central cystic degeneration, 15 mm in diameter, is reported. Contrast-enhanced computed tomography showed the tumor contained a central hypoattenuating region and had an irregular, heterogeneously enhanced wall. Magnetic resonance images showed a well-circumscribed lesion and the T(1)-weighted image indicated medium signal intensity, whereas the T(2)-weighted image indicated slight hypointensity. Both T(1)- and T(2)-weighted images showed central hyperintensity. Our preoperative diagnosis was renal cell carcinoma originating in a renal cyst wall or cystic renal cell carcinoma. Nephrectomy was performed because frozen-section examination did not completely rule out malignancy. The final pathological diagnosis of the entire surgical specimen was renal oncocytoma with cystic degeneration. To our knowledge, this is the 14th case of renal oncocytoma with central cystic degeneration reported in the published works. We discuss herein the variant forms of oncocytoma and difficulties with their preoperative diagnosis, especially when the tumor is small.     

Successful treatment of Rosai–Dorfman disease with low-dose oral corticosteroid

We present herein a Japanese case of Rosai–Dorfman disease (RDD) in which cutaneous manifestations completely remitted after treatment with low-dose oral corticosteroid. A 69-year-old Japanese man presented with a 1-year history of enlarged submandibular lymph nodes and subsequent nasal and pharyngeal bleeding. RDD was diagnosed based on biopsy results from a lymph node in the left parotid region. The patient had also noted several skin eruptions that repeatedly appeared and disappeared on the face and arms. Biopsies were taken from skin eruptions on the face and cuboidal fossa. Both biopsy specimens showed dense, well-demarcated infiltration of histiocytes, lymphocytes and multinucleated giant cells from just under the epidermis to the subcutaneous tissue. These histiocytes were positive for CD68 and S-100, but negative for CD1a, and some displayed emperipolesis. Given the histopathological findings and the fact that the patient was suffering from RDD, skin lesions were diagnosed as cutaneous manifestations of RDD. Cutaneous lesions gradually began to persist concomitant with enlargement of extranodal lymphadenopathy in the nasopharyngeal area. Increasing respiratory obstruction prompted a trial with oral prednisolone commencing at 0.4 mg/kg per day. Both the lymphadenopathy and skin lesions responded quickly. Within 3 months, all his skin lesions disappeared completely with almost complete resolution of lymphadenopathy. Twelve months after the beginning of oral prednisolone therapy, slight recurrence of mucosal and cutaneous lesions appeared, but disappeared quickly with an increase in prednisolone to 0.3 mg/kg per day. Low-dose prednisolone appeared very effective in the case of RDD.