Synthesis and photophysical properties of a bichromophoric system hosting a disaccharide spacer.

The synthesis of an efficient energy donor-acceptor system is reported, together with its photophysical properties. The bichromophoric species has been conceived to show potentialities for biological applications since a biocompatible disaccharide spacer, constituted of d-galactose and d-glucose derivatives, was used in compound 12 to connect two BODIPY units with different absorption/emission properties. The luminescence spectrum in acetonitrile of 12 shows an intense fluorescence band with a maximum at about 770 nm that is almost identical to that of the lowest-energy BODIPY, regardless of the excitation wavelength used. The quantum yield is 0.2 with an excited state lifetime of 2.5 ns. Excitation and ultrafast transient absorption spectroscopy demonstrates that a very efficient energy transfer takes place in 12 from the highest-energy lying BODIPY subunit to the lowest-energy emissive BODIPY moiety, with a time constant of about 31 ps. Noteworthily, the emission of 12 falls in the near infrared window, suitable for potential biological applications.

A Bodipy as a luminescent probe for detection of the G protein estrogen receptor (GPER).

We report the rational design, based on docking simulations, and synthesis of the first fluorescent and selective probe of GPER for bioimaging purposes and functional dissecting studies. It has been conceived as a Bodipy derivative and obtained by accessible and direct synthesis. Its optical properties have been measured in different solvents, showing insensitivity to their polarity. Its binding to GPER was achieved by competition assays with [3H]E2 and [5,6-3H] nicotinic acid in ER-negative and GPER-positive SkBr3 breast cancer cells. SkBr3 cells, transfected with a GPER expression vector containing a FLAG tag, were used to confirm that the fluorophore binds to GPER in a specific manner.

Erythema annulare centrifugum: report of a case with neonatal onset.

Darier's erythema annulare centrifugum (EAC) is often associated with infectious, autoimmune or neoplastic disease, nevertheless, most cases of EAC remain unexplained. We report a case of EAC with neonatal onset and a clinical course of over 20 years. The patient presented from the 6th day of life with erythematous papules that enlarged centrifugally to form figurate, annular or policyclic plaques involving the entire cutaneous surface. The clinical picture had a chronic course, disappearing only during unrelated febrile episodes. Histologic examination revealed a normal epidermis and a dense perivascular lymphohistiocytic infiltrate and numerous eosinophils in the superficial and reticular dermis. Today the patient is 24 years old and his lesions are still unchanged. Recently, clinical evaluation revealed a diffuse sderodermic induration. A second biopsy showed a diffuse thickening of collagen fibers in the dermis. To our knowledge, this is the second report of EAC with neonatal onset and such a long and peculiar clinical course.

Management of high-risk melanoma.

Improved treatment options for patients with high-risk melanoma are of great importance for clinicians who participate in the care of these patients. There remains an overall lack of response to existing treatment options, which continues to fuel the efforts of basic scientists and clinicians to pursue other approaches for the treatment of melanoma that is no longer limited to the skin. Continued investigation into the innovative and concurrent use of surgery, chemotherapy, immunotherapy, and radiation therapy holds significant promise for improved outcomes in the management of patients with this devastating disease.

beta-Sulfinyl alpha,beta-unsaturated carbonyl compounds from enantiomerically pure sulfenic acids.

The addition of enantiopure sulfenic acids to oxoalkynes constitutes a new and efficient methodology for the synthesis of beta-sulfinyl alpha,beta-unsaturated carbonyl compounds. Sulfenic acids 3 and 4 were generated by thermolysis of suitable precursors and trapped in situ by oxoalkynes 5, affording (R(S),E)- and (S(S),E)-3-alkylsulfinyl-1-phenyl-2-propen-1-ones, 4-alkylsulfinyl-3-buten-2-ones, and 3-[(1S)-isoborneol-10-sulfinyl]-2-propenoates 6 and 7 in good yields and in enantiomerically pure form after simple column chromatography. (R(S),E)-3-[(1S)-isoborneol-10-sulfinyl]-1-phenyl-2-propen-1-one (6(R)a) was involved as a heterodiene in inverse-electron-demanding Diels-Alder reactions with readily available electron-rich dienophiles 14 and 15, corroborating in each case the sulfinyl auxiliary capability in controlling the stereochemical outcome of these cycloadditions. Furthermore, the addition of methylmagnesium iodide to the carbonyl moiety of 6(R)a demonstrated that the chiral sulfur atom exerts a remote stereocontrol in this reaction if assisted by the hydroxy group being part of the isoborneol substituent.

Neutral endopeptidase terminates substance P-induced inflammation in allergic contact dermatitis.

Sensory nerve-derived neuropeptides such as substance P demonstrate a number of proinflammatory bioactivities, but less is known about their role in inflammatory skin disease. The cell surface metalloprotease neutral endopeptidase (NEP) is the principal proteolytic substance P-degrading enzyme. This study tests the hypothesis that the absence of NEP results in dysregulated inflammatory skin responses. The effector phase of allergic contact dermatitis (ACD) responses was examined in NEP(-/-) knockout and NEP(+/+) wild-type mice and compared with the irritant contact dermatitis response in these animals. NEP was found to be normally immunolocalized in epidermal keratinocytes and dermal blood vessels. The ACD ear swelling response was 2.5-fold higher in animals lacking NEP and was accompanied by a significant increase in plasma extravasation and infiltration of inflammatory leukocytes. The augmented ACD response in NEP(-/-) animals was abrogated by either administration of a neurokinin receptor 1 antagonist or by repeated pretreatment with topical capsaicin. Similar to NEP(-/-) mice, the acute inhibition of NEP in NEP(+/+) animals resulted in an augmented ACD response. In contrast to the ACD responses, little differences were observed in the irritant contact dermatitis response of NEP(-/-) compared with NEP(+/+) animals after epicutaneous application of the skin irritants croton oil or SDS. Thus, these results indicate that NEP and cutaneous neuropeptides have a significant role in the pathogenesis of ACD.

["Functional" neurovascular decompressive surgery of cranial rhino- base in headaches with rhinogenic triggering]. / La chirurgia "funzionale" decompressiva neurovascolare della rino-base cranica nelle cefalee primarie con trigger rinogeno.

Today one must include neurovascular decompression of the rhino-cranial base among the various forms of functional nasal surgery and the classical chapter on "Cephalea of rhinological origin" must be reviewed. In fact, all those forms of "apparently primary" headaches (i.e. migraine with and without aura, cluster headache, chronic paroxysmal migraine, tension headache) which have a central-peripheral etiopathogenesis due to a documented (CT) reduction in the volume of the "subcribriform ethmoid-sphenoidal chambers" affecting the hemoangiokinetics of endo-exocranial anastomotic circulation in this area. Rhino-cranial base neurovascular decompression surgery is described employing a "septo-ethmoid-sphenectomy". This surgery can either be conservative or radical, reaching the third degree monolateral with selective trigeminal-vegetative deafferentiation; this makes it possible to save the sense of smell, resolve the controlateral pain by decompressing the blood flow and even eliminate controlateral stasis. In addition, in a high percentage of cases, symptoms of neurological deficit or central irritation (i.e. visual aura, senso-motory palsy, epilepsy) disappear or are markedly improved after surgical elimination of the "peripheral rhinogenetic trigger". In a sample of 1000 of the 2124 patients who had undergone surgery from 1964 through the end of 1994, yearly follow-ups indicated that surgery cured or substantially improved 88%. On the other hand in 204 patients with similar forms of cephalea in advanced prophylaxis, 98% showed healing with "rapid disjunction of the palate" through "ortognatorhinodoncy" aimed at decompressing the neurovascular structure of the subcribrose chamber.

[Decompressive neurovascular nose and skull-base surgery in primary headache with a rhinogenic trigger]. / La chirurgia decompressiva neurovascolare della rino-base cranica nelle cefalee primarie con trigger rinogeno.

The therapeutical results such as recoveries or substantial improvements obtained by neurovascular decompressive functional morpho-corrective rhino-skull base surgery on 2124 cases of primary headaches (migraine with aura, migraine without aura, cluster headache, chronic paroxysmal hemicrania, tension-type headache) obliges a thorough review of the classical chapter on "rhinogenous headaches" (Bonaccorsi, Novak, Blondiau, Bisschop, Hoover, Clerico). In fact all those headaches seemingly "primary", but having a "central-peripheral" etiopathogenesis proved by a well documented (CT) volumetric reduction of "ethmoidosphenoidal subcribriform chamber" according to hemoangiokinetics purposes of endo-exocranial anastomotic circulation of this area, should be included in the chapter of "rhinogenous headaches". This endo-exocranial anastomotic circulation is considered a "functional unit" owing to the continuity of rhino-ophthalmic-encephalic trigeminal-vegetative and vascular circuits (Hannerz, Hardebo, Moskowitz). These morphological abnormalities of the rhino-skull base osteo-vascular-mucous structures acquire physio-pathological significance only in patients with "low pain threshold and elevated central integrative capability", modulated and timed by the neurogenic biorhythms. It is described the surgery of rhino-skull base by "neurovascular decompressive septo-ethmoidosphenoidectomy" procedure, either conservative or radical till the III grade monolateral with trigeminal and vegetative selective neurotomy that permits to save olfaction and to remove even the controlateral pain decompressing the circulation and eliminating stasis even on the opposite side. Further, it is emphasized that the neurological deficit or central irritative symptomatology (visual aura, sensory-motor paresis, epilepsy) disappears after surgical removal of the "peripheral rhinogenous trigger". It demonstrates a cause and effect relationship that is the central peripheral functional interdependence, even if it's included in the neuro-transmissive, biochemical, neuro-endocrine, constitutional background which is controlled by the psychical, vegetative and dysnociceptive biorhythms.

Treatment of cutaneous and pulmonary sarcoidosis with thalidomide.

Many therapeutic agents have been proposed for treatment of steroid-resistant sarcoidosis. Because administration of low doses of thalidomide has been successful in treating other inflammatory diseases, it was used in a patient with systemic sarcoidosis who was unresponsive to corticosteroids and in a patient with pulmonary sarcoidosis, in whom Kaposi's sarcoma developed after a course of corticosteroid therapy. Thalidomide, 200 mg/day for 2 weeks followed by 100 mg/day for 11 weeks, was given. This treatment was effective in both patients. No adverse reactions were observed. Thalidomide, 100 mg on alternate days, is still being administered. No relapse has occurred. Thalidomide, particularly because of its inhibition of the macrophage function, may be a useful alternative therapy in steroid-resistant cases. In addition, the correlation between the angiotensin-converting enzyme level and the clinical improvement observed in our patients suggests a direct parallel between angiotensin-converting enzyme and the activity of the granulomatous process.

Effects of the mode of delivery on ANP and renin-aldosterone system in the fetus and the neonate.

Plasma ANP and aldosterone levels, plasma renin activity (PRA), haematocrit, systolic and diastolic blood pressure (BP), were evaluated in 15 full-term infants delivered by elective Caesarean section (CS group) and in 15 full-term infants delivered vaginally (vaginal group). The mode of delivery did not influence the cord blood levels of ANP and their increase at the 24th hour of life. Instead, PRA was lower and plasma aldosterone levels were higher in the CS group than in the vaginal group. Also haematocrit and BP were influenced by mode of delivery. The haematocrit values were lower in the CS group than in the vaginal group at birth as well at the 24th hour of life. The values of systolic and diastolic BP were the same in both groups, at birth, but at the 24th hour of life increases were observed only in the vaginal group. On the fourth day of life weight loss was the same in both groups. Our findings suggest that the mode of delivery has more influence on neonatal BP adaptation than on neonatal volume homeostasis.

Atrial natriuretic peptide and renin-aldosterone relationship in healthy newborn infants.

Plasma atrial natriuretic peptide (ANP) and aldosterone concentrations, and plasma renin activity (PRA) were measured by radioimmunoassay concurrently in 20 healthy full term infants, in cord blood, at 24 hours after birth and on the 4th day of life. ANP and aldosterone increased significantly at 24 hours and was persistently elevated on the 4th day of life. PRA remained unchanged during the first four days of life. In cord blood, ANP concentrations were correlated with aldosterone concentrations (r = 0.49, p less than 0.05) and hematocrit (r = 0.58, p less than 0.02). At the 24 hours of life, plasma ANP concentrations were correlated with weight loss observed on the 4th day of life (r = -0.70, p less than 0.005), while the percentage changes in plasma aldosterone concentrations were correlated with percentage changes in systolic blood pressure (BP) (r = 0.49, p less than 0.05). These findings suggest that during the early newborn period ANP and aldosterone act as an integrated system which has a role in regulation blood pressure and intravascular volume homeostasis.