Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes

About a decade ago, cell membranes from the electric organ of Torpedo and from the rat brain were transplanted to frog oocytes, which thus acquired functional Torpedo and rat neurotransmitter receptors. Nevertheless, the great potential that this method has for studying human diseases has remained virtually untapped. Here, we show that cell membranes from the postmortem brains of humans that suffered Alzheimer's disease can be microtransplanted to the plasma membrane of Xenopus oocytes. We show also that these postmortem membranes carry neurotransmitter receptors and voltage-operated channels that are still functional, even after they have been kept frozen for many years. This method provides a new and powerful approach to study directly the functional characteristics and structure of receptors, channels, and other membrane proteins of the Alzheimer's brain. This knowledge may help in understanding the basis of Alzheimer's disease and also help in developing new treatments.     

Renin angiotensin system-regulating aminopeptidase activities in serum of pre- and postmenopausal women with breast cancer

Angiotensin peptides regulate vascular tone and natriohydric balance through the renin angiotensin system (RAS) and are related with the angiogenesis which plays an important role in the metastatic pathway. Estrogen influences the aminopeptidases (APs) involved in the metabolism of bioactive peptides of RAS through several pathways. We analyze RAS-regulating AP activities in serum of pre- and postmenopausal women with breast cancer to evaluate the putative value of these activities as biological markers of the development of breast cancer. We observed an increase in aminopeptidase N (APN) and aminopeptidase B (APB) activities in women with breast cancer; however, a decrease in aspartyl-aminopeptidase (AspAP) activity in premenopausal women. These results suggest a slow metabolism of angiotensin II (Ang II) to angiotensin III (Ang III) in premenopausal women and a rapid metabolism of Ang III to angiotensin IV (Ang IV) in pre- and postmenopausal women with breast cancer. An imbalance in the signals activated by Ang II may produce abnormal vascular growth with different response between pre- and postmenopausal women depending on the hormonal profile and the development of the disease.     

Case report. Primary mucosa-associated lymphoid tissue lymphoma as a pleural mass

Primary pleural lymphoma is a rare entity that has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. It occurs in only 7% of primary lymphoma cases. We report the case of a 52-year-old male with no history of HIV infection or pyothorax who was diagnosed of obstructive sleep apnoea syndrome (OSAS) and underwent a routine chest X-ray to screen for any organic cause of the symptoms. The radiograph revealed two voluminous masses with extraparenchymatous features but without pleural effusion. A contrast-enhanced CT was performed and confirmed the existence of the pleural masses that showed homogeneous attenuation. Neither mediastinal lymphadenopathy nor pleural effusion were present. A percutaneous CT-guided fine needle aspiration cytology (FNAC) with a 25-G needle was performed (two samples were obtained) and the first diagnosis was of non-Hodgkin's lymphoma. The final diagnosis of primary pleural mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by a CT-guided core biopsy with a 20-G needle. To the best of our knowledge, no cases of MALT lymphoma presenting as pleural masses without pleural effusion have been reported in immunocompetent patients. In this report, we describe the case of a patient with a primary pleural MALT lymphoma and include a short review of the literature.     

Roberto Caldeyro Barcia (1921-96): establishing the basis of modern obstetric physiology

Physicians have used fetal heart monitoring for 300 years but it has faced a revolution in the last 50 years after the incorporation of new devices and the discovery of the normal patterns of labour. Dr Caldeyro Barcia in Uruguay was one of the pioneers of the development of intrauterine pressure monitors and, with Dr Edward H Hon (1917-2007), he established the basis of modern electronic fetal heart monitoring which is still used in most labour and delivery rooms across the World. Nowadays medicine and technology advances so fast that devices created 10 years ago are considered old fashioned or obsolete.     

Quantitative correlations among CYP3A sensitive substrates and inhibitors: literature analysis

As a follow-up to the new classification of CYP3A inhibitors, the present work was undertaken to search for quantitative correlations of AUC ratios between sensitive substrates and midazolam (reference). A large set of clinical studies was obtained utilizing the M&T Drug Interaction Database, and recent Product Labels. Linear relationships were found between midazolam and four CYP3A substrates: simvastatin, buspirone, triazolam and eplerenone. Simvastatin and buspirone were consistently more sensitive than midazolam, independent of the inhibitor. Quantitative correlations of AUC ratios between four CYP3A inhibitors (fluconazole, erythromycin, verapamil, diltiazem) and ketoconazole (400 mg/day) were also uncovered. The average potencies of these inhibitors relative to ketoconazole were 27% for erythromycin, 17% for fluconazole and 19% for verapamil.     

Gigantic tongue lipoma: a case report

Lipomas are among the most common tumors of the human body. However, they are uncommon in the oral cavity. In the oral cavity they present as a slow growing, painless, and asymptomatic yellowish submucosal mass. Surgical excision is the treatment of choice with recurrence not expected. They have been known to grow to large sizes causing mastication and speech difficulties. The usual lesions consist of a well circumscribed, lobulated mass of mature fat cells. In other situations the covering mucosa becomes ulcerated and presents difficulties in diagnosis. The present report is of a patient who presented with a gigantic lipoma on the tip of the tongue which had been present for 3 years. She now had difficulty with speech and mastication as the tongue tumor now completely filled the oral cavity. An incision biopsy confirmed the tumor as lipoma. The tumor was surgically excised with restoration of normal tongue function, speech and masticatory capacity. Histopathologic examination of the excised tumor confirmed that it was a lipoma.     

A comparative study of oxycodone and morphine in a multi-modal, tissue-differentiated experimental pain model

Visceral pain can be difficult to treat with classical mu-opioid agonists and it has been suggested to use opioids with distinct pharmacological profiles. In animal experiments, oxycodone has shown different effects compared to morphine, and clinical observations have shown that oxycodone may occasionally be superior to, e.g., morphine in the treatment of visceral pain. In the current study, we randomised 24 healthy subjects to treatment with either morphine (30 mg), oxycodone (15 mg) or placebo in a crossover study. The experimental pain model involved multi-modal (mechanical, thermal and electrical) pain tests in the skin, muscles and viscera. The pain tests were carried out at baseline and 30, 60 and 90 min after oral administration of the drugs. The model showed effect of the two opioids compared to placebo on all stimulus modalities in all three types of tissues (all P values <0.001). Both opioids attenuated the sensory response mainly to painful stimulations. Morphine and oxycodone were equipotent in pain modulation of the skin and muscles, but oxycodone had superior analgesic effect to both morphine and placebo on the mechanical (P<0.001) and thermal (P<0.001) stimulations of the oesophagus. In conclusion, the multi-modal and tissue-differentiated pain model could link findings from animal experiments to clinical findings. A different pharmacological profile of oxycodone compared to that of morphine was shown, and thus oxycodone may be a useful alternative to morphine in the treatment of visceral pain syndromes.     

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer

Purpose

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin–angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers.

Methods

We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline.

Results

When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth.

Conclusion

Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment.