Nandrolone Supplementation Promotes AMPK Activation and Divergent 18[FDG] PET Brain Connectivity in Adult and Aged Mice.

Decreased anabolic androgen levels are followed by impaired brain energy support and sensing with loss of neural connectivity during physiological aging, providing a neurobiological basis for hormone supplementation. Here, we investigated whether nandrolone decanoate (ND) administration mediates hypothalamic AMPK activation and glucose metabolism, thus affecting metabolic connectivity in brain areas of adult and aged mice. Metabolic interconnected brain areas of rodents can be detected by positron emission tomography using 18FDG-mPET. Albino CF1 mice at 3 and 18 months of age were separated into 4 groups that received daily subcutaneous injections of either ND (15 mg/kg) or vehicle for 15 days. At the in vivo baseline and on the 14th day, brain 18FDG-microPET scans were performed. Hypothalamic pAMPKT172/AMPK protein levels were assessed, and basal mitochondrial respiratory states were evaluated in synaptosomes. A metabolic connectivity network between brain areas was estimated based on 18FDG uptake. We found that ND increased the pAMPKT172/AMPK ratio in both adult and aged mice but increased 18FDG uptake and mitochondrial basal respiration only in adult mice. Furthermore, ND triggered rearrangement in the metabolic connectivity of adult mice and aged mice compared to age-matched controls. Altogether, our findings suggest that ND promotes hypothalamic AMPK activation, and distinct glucose metabolism and metabolic connectivity rearrangements in the brains of adult and aged mice.

SEVERE LEUKOCYTOCLASTIC VASCULITIS AFTER COVID-19 VACCINATION - CAUSE OR COINCIDENCE? CASE REPORT AND LITERATURE REVIEW.

Vaccination has been the most powerful tool to fight the COVID-19 pandemic while the specific treatment options in clinical practice have been under review for approval and authorization by regulatory bodies. After registration of different vaccines, it is important to ensure a post-marketing surveillance to identify potential risks not observed in controlled trials. Authors report on the case of an 80-year-old male patient who developed severe leukocytoclastic vasculitis of skin and oral mucous membrane after receiving the second dose of COVID-19 mRNA vaccine. He was treated successfully with prednisolone. We also provide a literature review on other reported cases of COVID-19 vaccine induced vasculitis. This type of an adverse reaction seems to be rare. Fortunately, most cases were temporary and well controlled by corticosteroids. The majority of vaccine-associated vasculitis cases have been observed in association with BONT162b2 mRNA vaccine although other vaccines also may cause the event. The knowledge of this possible adverse event is important for early diagnosis and intervention.

CUTANEOUS POLYPOID MELANOMA OF HEAD AND NECK.

Cutaneous polypoid melanoma is an uncommon subtype of malignant melanoma. The clinical behavior of this subtype has been described as aggressive. Tumors can be sessile or pedunculated. The typical patient is a younger adult. Authors have analyzed the case histories of patients with polypoid melanomas of the head and neck region treated at our clinic from 2001 to 2018. We identified 3 female patients with tumors of the neck and cheek. In contrast to other reports, all patients were older than 80-years of age. None of them had a metastatic spread at the time of diagnosis. Treatment was delayed Mohs surgery. Polypoid melanomas of the head and neck region can occur in elderly patients without an aggressive course. In those patients a number of differential diagnoses have to be considered including Merkel cell carcinoma, metatypical basal cell carcinoma, squamous cell carcinoma and tumor metastases.

PEMETREXED-INDUCED PSEUDOCELLULITIS - A RARE CUTANEOUS ADVERSE REACTION TO MULTI-TARGETED ANTIFOLATE THERAPY.

Pemetrexed is a multi-targeted folate antagonists approved for non-small cell lung cancer and other malignancies. Adverse cutaneous reactions have been reported in up to 1/3 of patients treated. A rare cutaneous adverse reaction is pseudocellulitis. We report about a 62-year-old male patient treated with a combination of cisplatin and pemetrexed for non-small cell lung cancer stage IV who developed about 4 months after initiation of treatment painful, non-febrile erythematous lesions on feet and lower legs. There was no lymphadenopathy and no general malaise. Laboratory investigations detected increased level of C-reactive protein but normal values of procalcitonin. A skin biopsy revealed a mild interface dermatitis. Antifolate treatment was stopped and he received oral and topical corticosteroids, compression therapy and supplementation with folate and vitamin B. A complete remission of skin eruptions was achieved. Pemetrexed-induced pseudocellulitis is a possible, but rare complication of treatment that oncologists and dermatologists should know. Systemic antibiosis is unnecessary.

Guanosine Exerts Neuroprotective Effect in an Experimental Model of Acute Ammonia Intoxication.

The nucleoside guanosine (GUO) increases glutamate uptake by astrocytes and acts as antioxidant, thereby providing neuroprotection against glutamatergic excitotoxicity, as we have recently demonstrated in an animal model of chronic hepatic encephalopathy. Here, we investigated the neuroprotective effect of GUO in an acute ammonia intoxication model. Adult male Wistar rats received an intraperitoneal (i.p.) injection of vehicle or GUO 60 mg/kg, followed 20 min later by an i.p. injection of vehicle or 550 mg/kg of ammonium acetate. Afterwards, animals were observed for 45 min, being evaluated as normal, coma (i.e., absence of corneal reflex), or death status. In a second cohort of rats, video-electroencephalogram (EEG) recordings were performed. In a third cohort of rats, the following were measured: (i) plasma levels of glucose, transaminases, and urea; (ii) cerebrospinal fluid (CSF) levels of ammonia, glutamine, glutamate, and alanine; (iii) glutamate uptake in brain slices; and (iv) brain redox status and glutamine synthetase activity in cerebral cortex. GUO drastically reduced the lethality rate and the duration of coma. Animals treated with GUO had improved EEG traces, decreased CSF levels of glutamate and alanine, lowered oxidative stress in the cerebral cortex, and increased glutamate uptake by astrocytes in brain slices compared with animals that received vehicle prior to ammonium acetate administration. This study provides new evidence on mechanisms of guanine-derived purines in their potential modulation of glutamatergic system, contributing to GUO neuroprotective effects in a rodent model of by acute ammonia intoxication.

[Disseminated necrobiotic xanthogranuloma]. / Disseminiertes nekrobiotisches Xanthogranulom.

Necrobiotic xanthogranuloma is a rare non-Langerhans-cell histiocytosis. A 62-year-old woman presented with yellowish erythematous plaques, nodules, and papules in the periorbital region and the extremities. She had a nodular tumor grown on the left upper lid that clinically resembled a keratoacanthoma. Histologically it was a xanthogranulomatous lesion. She suffered from monoclonal gammopathy of unknown significance of κ­type. Treatment was realized with a combination of systemic dapsone/prednisolone and topical corticosteroids.

Generalized eruptive histiocytoma in adult patient.

Generalized eruptive histiocytoma is a rare benign skin disorder with less than 50 cases reported world-wide. It belongs to type IIb of histiocytoses. The histiocytic cells are CD68 positive but lack other markers like CD1a or S100. We report on a 60-year-old male patient with generalized eruptive histiocytoma treated successfully by PUVA combined with topical corticosteroids.

Failure of vismodegib in advanced Basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common malignant tumor of mankind. For locally advanced and metastatic BCC treatment options are limited. Recently, the first hedgehog signal pathway inhibitor, vismodegib, has been approved for such tumors. Although high response rates have been reported for spontaneous BCC and Gorlin-Goltz syndrome, some tumors do not respond primarily or secondarily. We report about a 38-year-old female patient with a large multicentric BCC of temple with primary chemoresistance of the tumor. We discuss possible mechanism and other limitations of vismodegib in BCC.

Neuroprotective effects of guanosine administration on behavioral, brain activity, neurochemical and redox parameters in a rat model of chronic hepatic encephalopathy.

It is well known that glutamatergic excitotoxicity and oxidative stress are implicated in the pathogenesis of hepatic encephalopathy (HE). The nucleoside guanosine exerts neuroprotective effects through the antagonism against glutamate neurotoxicity and antioxidant properties. In this study, we evaluated the neuroprotective effect of guanosine in an animal model of chronic HE. Rats underwent bile duct ligation (BDL) and 2 weeks later they were treated with i.p. injection of guanosine 7.5 mg/kg once a day for 1-week. We evaluated the effects of guanosine in HE studying several aspects: a) animal behavior using open field and Y-maze tasks; b) brain rhythm changes in electroencephalogram (EEG) recordings; c) purines and glutamate levels in the cerebral spinal fluid (CSF); and d) oxidative stress parameters in the brain. BDL rats presented increased levels of glutamate, purines and metabolites in the CSF, as well as increased oxidative damage. Guanosine was able not only to prevent these effects but also to attenuate the behavioral and EEG impairment induced by BDL. Our study shows the neuroprotective effects of systemic administration of guanosine in a rat model of HE and highlights the involvement of purinergic system in the physiopathology of this disease.

Cutaneous angiosarcoma is a rare aggressive malignant vascular tumour of the skin.

BACKGROUND: Cutaneous angiosarcoma (AS) is a rare aggressive malignant vascular tumour of the skin. METHODS: We analysed the cases of cutaneous AS in two large dermatological departments of Saxony during the last 10 years. RESULTS: A total of eight AS cases were identified, mostly with head and neck involvement. Because of age and late diagnosis, only a minor part was completely resectable. As a palliative therapy pegylated liposomal doxorubicin was used. The drug was well tolerated. Our cases and those published in the literature suggest a high rate of responses and a possible sensitisation to subsequent radiation therapy. CONCLUSIONS: Although complete surgical resection followed by wide-field radiation therapy has been established as a therapeutic standard for AS, delay in diagnosis and older age with comorbidities warrant for a safe and effective adjuvant treatment. Pegylated liposomal doxorubicin combined with radiotherapy seems to be a useful and safe alternative.

Late recurrence (10 years or more) of malignant melanoma in south-east Germany (Saxony). A single-centre analysis of 1881 patients with a follow-up of 10 years or more.

BACKGROUND: Late recurrent melanoma (MM) is rare. OBJECTIVE: In the present study, we analysed the frequency of late recurrent MM in south-eastern Germany. PATIENTS AND METHODS: In our centre, 2314 MM patients were documented (1972-2001). A total of 1881 patients in stage I or II (AJCC) with a follow-up of > or = 10 years were selected and screened for late recurrence (> or = 10 years after diagnosis). RESULTS: Twenty patients were identified (1.1%), 13 women and 7 men, median age 44 years (age range 30-74 years). Nineteen suffered from cutaneous MM and one had a uveal MM (excluded from further analysis). The primary cutaneous MM occurred on the trunk (6), on the upper limb/shoulder (4), or on the lower limb (9). MM type was superficial spreading (13), nodular (2), acrolentiginous (1), lentigo maligna-type (1) or unclassified (2). Tumour thickness varied from 0.33 mm to 9.5 mm (median 2.0 mm). Ulceration was seen in four, and spontaneous regression in two MM patients. Invasiveness into blood or lymphatic vessels occurred in seven MM patients. The largest period from primary diagnosis to recurrence was 25.1 years with a median of 13.9 years. Metastatic spread was loco-regional (12 patients) or distant (7). Four patients were survivors and three of these had in-transit metastases only. Overall survival was 14.7 +/- 6.6 years. Statistical analysis could not identify factors significantly associated with late recurrence. CONCLUSIONS: Late recurrence is a clinical sign of melanoma dormancy. We conclude that late recurrences argue for a lifelong follow-up of melanoma patients.

Using VAC to facilitate healing of traumatic wounds in patients with chronic lymphoedema.

Healing of traumatic injuries in patients with chronic lymphoedema is often delayed. This article describes how topical negative pressure was used to promote healing in two such cases. It also eliminated pain and prevented re-infection.

The use of topical calcineurin inhibitors in lupus erythematosus: an overview.

Lupus erythematosus (LE) shows a broad range of cutaneous symptoms, including acute, subacute and chronic lesions. The gold standard of established topical treatment consists of medium- to high-potency corticosteroids. Because face and neck are often involved, adverse effects of prolonged corticosteroid use are not uncommon. There is a need of steroid-free topical treatment in LE. With the development of topical calcineurin inhibitors, tacrolimus and pimecrolimus, there is an alternative available. The present study reviews the literature data on topical tacrolimus and pimecrolimus for malar rash, subacute lesions and discoid chronic lesions among others. The present data argue for an efficacy of these compounds in acute and subacute cutaneous LE manifestations with a rapid response and only minor side-effects when used as an adjunct to systemic treatment. In chronic discoid LE, hypertrophic plaques do not well respond because of limited penetration. The primary target seems to be the decrease or blocking of cytokine production by activated T lymphocytes.

[120 years Dresden-Friedrichstadt Dermatology Clinic]. / 120 Jahre Hautklinik Dresden-Friedrichstadt.

The dermatology clinic in Dresden-Friedrichstadt this year celebrates 120 years of existence. It is one of the oldest dermatology clinics in Germany. The contribution presents an overview of the major events from the clinic's foundation as "External Section for Dermal and Venereal Diseases and Minor Surgery" in 1874 up to the present time. The clinic has played an important part in the development of the field of dermatology in Dresden. A brief account of the most important medical superintendents and of their scientific activities is given.

Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM).

Six months monotherapy with Acarbose vs. glibenclamide led to a marked improvement of BG and HbA1 in NIDDM, insufficiently controlled with diet. Beneficial effects of these distinct principles of action were statistically not different.

[An investigation into the levels of a trimethoprim-sulphamethoxazole combination in the ventricular fluid of neurosurgical patients (author's transl)]. / Liquorspiegel-Untersuchungen einer Trimethoprim-Sulfamethoxazol-Kombination im Ventrikelliquor bei neurochirurgischen Patienten.

Results of measurements of Trimethoprim-Sulphamethoxazole (Bactrim, Eusaprim) levels in the CSF of seven patients with intact meninges are reported. The maximum fluid concentration of non-protein-bound SMZ was approximately 46.5%. The TMP value was 68.9%. With this combination of drugs it is possible to achieve a high CSF level of broadspectrum chemotherapeutic substances in neurosurgical patients.

[The microsurgical treatment of the so-called tuberculum-sellae-meningiomas (author's transl)]. / Die mikrochirurgische Behandlung der sogenannten Tuberculum-sellae-Meningeome.

Experience from five cases operated on within one year (among 50 microsurgical operations at the base of the brain) persuades us to discuss the topical relations of the meningiomas of the tuberculum sellae and the modifications in operating techniques necessary. For the two contrasting types of tumour found, which are:-- 1. Tumours en plaque with osseous reactions, particularly of the sphenoidal ridge, in which the exact predetermination of the positions of the optic nerve and of the carotid artery is facilitated by means of measurement and by fronto-temporal approach (which does not preclude a frontal or a bifrontal approach). 2. Suprasellar tumours whose topical relationships to the posterior surface of the chiasma, the pituitary stalk, the big vessels, and the perforating arteries increase the risk of operation. Radical operations for tumours near the pituitary stalk are not always advisable. Pre- and postoperative analysis of the anatomical characteristics of the individual case is essential before microsurgical intervention.

Comparison of the effects of nitrogen mustard on the functional properties of mitochondria from sensitive and resistant strains of Ehrlich ascites tumors.

In vivo treatment of sensitive tumor cells with nitrogen mustard (HN2) results in marked inhibitions of protein and nucleic acid synthesis by mitochondria subsequently isolated from these cells. This inhibition occurs at doses of drug which produce no apparent inhibition of total RNA synthesis. The inhibition gradually reverses itself in sensitive cells and is less severe and more rapidly reversed in resistant cells. The in vivo sensitivity of the mitochondria is in striking contrast to their in vitro behavior; isolated mitochondria resist 50 times the in vivo ID50 level of the drug. The sensitivity of protein and RNA synthesis in mitochondria is presumed to be related to the differences in organization between the nucleocytoplasmic processes and the mitochondrial. But the data also suggest that the in vivo effects on mitochondria are indirect, either acting via the cytoplasm or nucleus or via a carrier mechanism having mitochondrial affinity.