Histochemistry of flight muscles in the Jamaican fruit bat, Artibeus jamaicensis: implications for motor control

Two fast-twitch fiber types are histochemically identified in the primary flight muscles of Artibeus jamaicensis. These are classified as type IIa and IIb according to an acid-preincubation staining protocol for myosin ATPase. All fibers in the bat flight muscles exhibit relatively intense staining properties for NADH-TR, suggesting a high oxidative capacity. The glycolytic potential of all fibers is rather low, as assessed by stains for alpha-GPD. This two-type histochemical profile appears to parallel biphasic electromyographic patterns observed in these muscles and leads us to propose that flight muscle histochemistry and activation are mediated by a "two-gear" neuromuscular control system. In contrast, earlier studies on Tadarida brasiliensis demonstrate the existence of a "one-gear" neuromuscular control system, exemplified by the presence of one fiber type. These observations are discussed with respect to the natural history and flight styles of several species.     

Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy

Introduction

Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy.

Methods

Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR.

Results

Among 212 patients randomized in the RCTs, 155 (73%) had ≥1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo).Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70% (39/56) of patients and 55% (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70% of tophi) than nonresponders (30/93; 32%).

Conclusions

Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy.

Trial registrations

{"type":"clinical-trial","attrs":{"text":"NCT00325195","term_id":"NCT00325195"}}NCT00325195, {"type":"clinical-trial","attrs":{"text":"NCT01356498","term_id":"NCT01356498"}}NCT01356498     

Sensory reinnervation and sensibility in skin transplants

Reinnervation and sensibility were investigated in patients previously subjected to split thickness skin transplantation after excision of skin and subcutaneous fat for treatment of malignant melanoma. All patients except one showed poor sensibility and no neurofilament positive sensory nerve fibres were detected. Most patients had heat and pain sensibility but with a higher threshold than on the control side. It is suggested that this heat pain sensibility is mediated from nerve fibres in the underlying tissue. In one patient, however, sensibility was encountered and in this patient neurofilament positive sensory nerve fibres were observed in the dermis and epidermis.     

Ontogeny of the Pectoralis muscle in the little brown bat,Myotis lucifugus

The ontogeny of a primary flight muscle, the pectoralis, in the little brown bat (Myotis lucifugus: Vespertilionidae) was studied using histochemical, immunocytochemical, and electrophoretic techniques. In fetal and early neonatal (postnatal age 1–6 days) Myotis, histochemical techniques for myofibrillar ATPase (mATPase) and antibodies for slow and fast myosins demonstrated the presence of two fiber types, here called types I and IIa. These data correlated with multiple transitional myosin heavy chain isoforms and native myosin isoforms demonstrated with SDS-PAGE and 4% pyrophosphate PAGE. There was a decrease in the distribution and number of type I fibers with increasing postnatal age. At postnatal age 8–9 days, the adult phenotype was observed with regard to muscle fiber type (100% type IIa fibers) and myosin isoform profile (single adult MHC and native myosin isoforms). This “adult” fiber type profile and myosin isoform composition preceeded adult function by about 2 weeks. For example, little brown bats were incapable of sustained flight until approximately postnatal day 24, and myofiber size did not achieve adult size until approximately postnatal day 25. Although Myotis pectoralis is unique in being composed of 100% type IIa fibers, transitional fiber types and isoforms were present. These transitional forms had been observed previously in other mammals bearing mixed adult muscle fibers and which undergo transitional stages in muscle ontogeny. However, in Myotis pectoralis, this transition transpires relatively early in development. © 1994 Wiley-Liss, Inc.     

Pectoralis muscle morphology in the little brown bat,Myotis lucifugus: A non-convergence with birds

Recent studies of muscle architecture demonstrate that many mammalian muscles are composed of short, interdigitating fibers. In addition, the avian pectoralis, a muscle capable of producing high frequency oscillations has been shown to possess a serially arranged pattern of muscle endplate in all sizes of birds studied. The pectoralis muscle of the little brown bat, Myotis lucifugus (Chiroptera: Vespertilionidae), is composed of fairly uniform fibers that span the length of the muscle and is characterized by a zone of motor endplates within the middle third of the muscle. The homogeneous fiber architecture of the bat pectoralis muscle is in contrast to the serial arrangement of endplates (and presumably muscle muscle fibers) in the avian pectoralis in species equivalent in size to Myotis. The short fiber organization and motor endplate pattern observed in most birds is thus not a requisite design for flying vertebrates. © 1994 Wiley-Liss, Inc.     

Phylogeny and biogeography of ratite birds inferred from DNA sequences of the mitochondrial ribosomal genes

The origin of the flightless ratite birds of the southern continents has been debated for over a century. Whether dispersal or vicariance (continental breakup) best explains their origin depends largely on their phylogenetic relationships. No consensus has been reached on this issue despite many morphological and molecular studies. To address this question further we sequenced a 2.8-kb region of mitochondrial DNA containing the ribosomal genes in representative ratites and a tinamou. Phylogenetic analyses indicate that Struthio (Africa) is basal and Rhea (South America) clusters with living Australasian ratites. This phylogeny agrees with transferrin and DNA hybridization studies but not with sequence analyses of some protein-coding genes. These results also require reevaluation of the phylogenetic position of the extinct moas of New Zealand. We propose a new hypothesis for the origin of ratites that combines elements of dispersal and vicariance.      

Morphology and histochemistry of the ambiens muscle of the red-eared turtle (Pseudemys scripta)

Six fiber types have been described in the ambiens muscle of red-eared turtles. These include one slow oxidative type, two fast oxidative types, two fast oxidative and glycolytic types, and one fast glycolytic type. Fiber types are non-randomly distributed throughout cross sections of the muscle. There is a decreasing gradient of oxidative staining and an increasing gradient of glycolytic staining along an axis from the superficial to deep regions of the muscle. The slow oxidative fibers are predominantly located within one or two fascicles of the superficial surface of the muscle. The fast glycolytic fibers are predominant in deep fascicles. In contrast to previous reports of histochemically monotypic intrafusal fibers in turtle muscle, ambiens muscle spindles have been observed containing one to eleven intrafusal fibers, including two fiber types. Fiber diameter and area are consistently smaller than observed in most extrafusal fibers. Spindles are predominantly located in superficial and cranial fascicles of the ambiens muscle and are located in regions characterized by extrafusal fibers with high oxidative activity.     

Histochemical and myosin composition of vampire bat (Desmodus rotundus) pectoralis muscle targets a unique locomotory niche

The vampire bat pectoralis muscle contains at least four fiber types distributed in a nonhomogeneous pattern. One of these fiber types, here termed IIe, can be elucidated only by adenosine triphosphatase (ATPase) histochemistry combined with reactions against antifast and antislow myosin antibodies. The histochemical and immunohistochemical observations indicate a well-developed specialization of function within specific regions of the muscle. In parallel, analyses of native myosin isoforms and myosin heavy chain isoforms indicate two points. First, the histochemical “type IIe” fiber is predominant in cranial portions of the muscle, and myosin extracted from these regions exhibits a unique electrophoretic mobility not observed in the myosin isoforms of more traditional laboratory mammals. Second, the type I fibers are confined to the pectoralis abdominalis muscle and a small adjacent region of the caudal part of the pectoralis. This pattern of type I fiber distribution is considered a derived character state compared to muscle histochemical phenotype and isoform composition in the pectoralis muscles of other phyllostomids we have studied (Artibeus jamaicensis, Artibeus lituratus, Carollia perspicillata). We relate this to the unique locomotory needs of the common vampire bat, Desmodus rotundus. © 1993 Wiley-Liss, Inc.