New synthetic pathway leading to oxospirochlorins

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The mechanism of reaction was analyzed employing theoretical methods by comparing the difference in energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between molecular structure and optical properties for the obtained title compounds is discussed.

Oxospirochlorins – novel analogs of porphyrinoids were synthesized and characterized by various methods including X-ray, NMR spectroscopy and mass spectrometry.     

“Salt mummification” — atypical method of embalming a corpse

International Journal of Legal Medicine - It is extremely rare for table salt to be used to preserve a dead body in criminal cases. In the case presented here, after the death of his 85-year-old...     

Secrets of success of a human pathogen: molecular evolution of pandemic clones of meticillin-resistant Staphylococcus aureus

The first European isolate of meticillin-resistant Staphylococcus aureus (MRSA) was detected in 1960. Since then MRSA has become a leading cause of nosocomial infections worldwide. Using molecular typing techniques--primarily pulsed-field gel electrophoresis (PFGE)--we identified five major MRSA clones that accounted for almost 70% of the over 3000 MRSA isolates recovered in hospitals mainly in southern and eastern Europe, South America, and the USA. Most of our surveillance studies were done in these areas. Multilocus sequencing typing (MLST) of representative isolates of this collection showed that these five pandemic MRSA clones have evolved from only two distinct ancestral genetic backgrounds, one of which can be traced back to the very first European MRSA isolates and also to meticillin susceptible S aureus strains circulating in Danish hospitals during the mid to late 1950s--i.e., shortly before the introduction of meticillin into therapy. The second lineage with a completely different MLST profile included MRSA frequently recovered in the USA, Japan, and among paediatric isolates from several parts of the world. A few isolates with a third distinct MLST type corresponding to that of EMRSA-16 were also detected in the early Danish isolates. The four structural types of mec element, the heterologous DNA segment containing the meticillin resistance determinant mecA, were present in unique combinations with the MRSA clonal types. Our findings establish evolutionary associations in the most widely spread pandemic clones of MRSA. The epidemiological factors that contributed to the massive dissemination of a few MRSA clones are not well understood. We suggest, however, that the secrets of effectiveness of MRSA could be hidden in the unique genetic background of a surprisingly few lineages of S aureus particularly well able to cope with the contemporary clinical environment.     

Steroid sex hormones and prolactin in postmenopausal women with generalized mammary carcinoma during prolonged dexamethasone treatment.

The endocrine response to prolonged dexamethasone treatment was investigated in six postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly and became undetectable whereas significant concentrations of plasma dehydroepiandrosterone and androstenedione persisted throughout the study, even in two ovariectomized patients, indicating a certain degree of autonomy or a greater resistance of adrenal 'androgens' to the inhibition of ACTH secretion. Except in the ovariectomized patients, plasma testosterone did not fall significantly whereas the plasma oestrogens tended progressively towards undetectable concentrations. A similar response was found in six normal postmenopausal women although the disappearance of their oestrogens was relatively rapid. This indicates that much of the testosterone present after the menopause could still be produced by the ovaries whereas the ovarian production of oestrogens becomes negligible. The delayed disappearance of oestrogens in the patients with mammary carcinoma indicates that the persisting adrenal 'androgens' remained efficient precursors of oestrogen synthesis within the peripheral tissues and presumably within the mammary tumour itself. Plasma dihydrotestosterone behaved like the plasma oestrogens. Despite the fall in plasma oestrogens, plasma gonadotrophins did not increase further but plasma prolactin rose progressively. The persistance of steroid sex hormones and the rise of plasma prolactin might explain the poor response to dexamethasone treatment in mammary carcinoma.     

Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Graves' Ophthalmopathy

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position -174 (G→C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P=0.35) and C/C genotype (20 vs 15%; P=0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P=0.76) and C/C genotype (20 vs 20%; P=0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.     

How Do Different Anterior Tibial Tendon Transfer Techniques Influence Forefoot and Hindfoot Motion?

Background

Idiopathic clubfoot correction is commonly performed using the Ponseti method and is widely reported to provide reliable results. However, a relapsed deformity may occur and often is treated in children older than 2.5 years with repeat casting, followed by an anterior tibial tendon transfer. Several techniques have been described, including a whole tendon transfer using a two-incision technique or a three-incision technique, and a split transfer, but little is known regarding the biomechanical effects of these transfers on forefoot and hindfoot motion.

Questions/purpose

We used a cadaveric foot model to test the effects of three tibialis anterior tendon transfer techniques on forefoot positioning and production of hindfoot valgus.

Methods

Ten fresh-frozen cadaveric lower legs were used. We applied 150 N tension to the anterior tibial tendon, causing the ankle to dorsiflex. Three-dimensional motions of the first metatarsal, calcaneus, and talus relative to the tibia were measured in intact specimens, and then repeated after each of the three surgical techniques.

Results

Under maximum dorsiflexion, the intact specimens showed 6° (95% CI, 2.2°–9.4°) forefoot supination and less than 3° (95% CI, 0.4°–5.3°) hindfoot valgus motion. All three transfers provided increased forefoot pronation and hindfoot valgus motion compared with intact specimens: the three-incision whole transfer provided 38° (95% CI, 33°–43°; p < 0.01) forefoot pronation and 10° (95% CI, 8.5°–12°; p < 0.01) hindfoot valgus; the split transfer, 28° (95% CI, 24°–32°; p < 0.01) pronation, 9° (95% CI, 7.5°–11°; p < 0.01) valgus; and the two-incision transfer, 25° (95% CI, 20°–31°; p < 0.01) pronation, 6° (95% CI, 4.2°–7.8°; p < 0.01) valgus.

Conclusion

All three techniques may be useful and deliver varying degrees of increased forefoot pronation, with the three-incision whole transfer providing the most forefoot pronation. Changes in hindfoot motion were small.

Clinical Relevance

Our study results show that the amount of forefoot pronation varied for different transfer methods. Supple dynamic forefoot supination may be treated with a whole transfer using a two-incision technique to avoid overcorrection, while a three-incision technique or a split transfer may be useful for more resistant feet. Confirmation of these findings awaits further clinical trials.