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The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung that can facilitate systemic delivery via pulmonary administration of peptides and proteins. Physical and biochemical barriers, lack of optimal dosage forms and delivery devices limit the systemic delivery of biotherapeutic agents by inhalation. Current efforts to overcome these difficulties in order to deliver metabolic hormones (insulin, calcitonin, thyroid-stimulating hormone [TSH], follicle-stimulating hormone [FSH] and growth hormones) systemically, to induce systemic responses (immunoglobulins, cyclosporin A [CsA], recombinant-methionyl human granulocyte colony-stimulating factor [r-huG-CSF], pancreatic islet autoantigen) and to modulate other biological processes via the lung are reviewed. Safety aspects of pulmonary peptide and protein administration are also discussed. [ABSTRACT FROM AUTHOR]

Abstract The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung that can facilitate systemic delivery via pulmonary administration of peptides and proteins. Physical and biochemical barriers, lack of optimal dosage forms and delivery devices limit the systemic delivery of biotherapeutic agents by inhalation. Current efforts to overcome these difficulties in order to deliver metabolic hormones (insulin, calcitonin, thyroid-stimulating hormone [TSH], follicle-stimulating hormone [FSH] and growth hormones) systemically, to induce systemic responses (immunoglobulins, cyclosporin A [CsA], recombinant-methionyl human granulocyte colony-stimulating factor [r-huG-CSF], pancreatic islet autoantigen) and to modulate other biological processes via the lung are reviewed. Safety aspects of pulmonary peptide and protein administration are also discussed.

We report a case of falsely elevated triiodothyronine (T3) due to anti-T3 antibody interference in two immunoassays (Cobas 8000 e602® module (Roche Diagnostics) and Architect® i2000 (Abbott)). The interference was investigated using various laboratory methods including the search for heterophilic antibodies, biotin detection and the polyethylene glycol precipitation of potential interfering macromolecules. The presence of anti-T3 autoantibodies was detected and measured by radioimmunoprecipitation. Our investigations confirmed the clinical suspicion of a falsely elevated free T3. No further explorations or unnecessary treatments were conducted for this patient after identification of the interference. This underlines the importance of implementing systematic analytical procedures in laboratories for the search of suspected interferences.

Background: Amyloid infiltration of endocrine glands has been reported, mostly in the thyroid, pancreas, adrenals, and testes, but affected patients do not frequently exhibit overt endocrine insufficiency. Here we report the case of a patient with complete anterior hypopituitarism probably due to a known systemic amyloidosis., Case Presentation: Our male Caucasian patient was diagnosed with Crohn's disease at the age of 22 years. At the age of 37, he developed secondary renal amyloidosis, which resulted in end-stage renal failure. He received a living-donor kidney transplant at the age of 57, without initial complication. Two months later, he developed extreme fatigue, weight loss, and dyspnea. A hormonal evaluation demonstrated complete anterior pituitary insufficiency. A pituitary magnetic resonance imaging was performed and showed a diffusely hypointense anterior gland on both T1-weighted and T2-weighted images with reduced gadolinium enhancement, highly suggestive of amyloid infiltration of the pituitary. Treatment was initiated with levothyroxine, orally administered hydrocortisone, and testosterone enanthate, rapidly allowing progressive marked clinical improvement and nearly complete resolution of symptoms., Conclusions: Pituitary amyloid infiltration should be considered in patients with a known systemic amyloidosis who develop symptoms of hypopituitarism and magnetic resonance imaging features compatible with protein deposits.

1 Direct myocardial effects of the S(-)- and R(+)-enantiomers of bupivacaine were compared in the guinea-pig isolated papillary muscle by recording transmembrane action potentials with the standard microelectrode technique. 2 In 5.4 mM K+, at a stimulation rate of 1 Hz, the maximal rate of depolarization (Vmax) was reduced to 59.9 +/- 1.4% (n = 10) of control (mean +/- s.e.mean) in the presence of 10 microM R(+)-bupivacaine, and to 76.7 +/- 1.2% (n = 14) in the presence of the same concentration of S(-)-bupivacaine. This was mainly due to a difference in time constant at which block dissipated during the diastolic period. Recovery was slower in the presence of R(+)-bupivacaine. The slower recovery in the presence of R(+)-bupivacaine resulted also in a more pronounced frequency-dependent block of Vmax. 3 Time constants for recovery from use-dependent block became significantly faster for both enantiomers on hyperpolarization, while no significant change was observed at depolarization. At all membrane potentials recovery was slower in the presence of R(+)-bupivacaine. 4 The action potential duration (APD) was shortened to a greater extent in the presence of R(+)-bupivacaine over a large range of stimulation frequencies. 5 We conclude that S(-)-bupivacaine affects Vmax and APD in the guinea-pig papillary muscle less than the R(+)-enantiomer at different rates of stimulation and resting membrane potentials.